Strategies To Maintain Optimal Bone Health

The Truth About Osteoporosis

Discover Easy Strategies To Maintain Optimal Bone Health And Reverse Osteoporosis. Here is a quick preview of the valuable information youll have at your fingertips: Statistics can lead to false conclusions. Bone Quality or Quantity? Density or Strength? Find what matters! What happens to unabsorbed calcium? How do prescribed medications fit in the equation? What is the 4-R Program and can it help reverse osteoporosis? What part does protein play in bone health? What contribution does lifestyle make? Am I unknowingly my own worst enemy? What about inflammation and stress? How do they impact my bones?Does an acidic system affect the progress of osteoporosis? Who would suspect this sneaky culprit (in your tap water) as contributing to loss of bone health? Discover 4 easy steps for relieving stress. What part do hormones play in osteoporosis? How to encourage new bone growth. Find 7 steps to a workable exercise program. Look at the whole body. 12 steps to changing habits effortlessly.

The Truth About Osteoporosis Summary


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Thyroid Disease and Osteoporosis

Women who take thyroid hormone commonly ask about the link between thyroid disease and osteoporosis. (As mentioned earlier, contrary to what most women think, the link has nothing to do with calcitonin, which the thyroid also produces, as discussed in Chapter 1.) A particular risk for people with thyroid cancer is loss of parathyroid hormone from accidentally damaging the parathyroid glands during thyroid surgery (see Chapter 11). There are further complications with osteoporosis discussed in Chapter 11, which explains treatment for hypoparathyroidism or low-functioning parathyroid glands.


Osteoporosis is a common problem among seniors, affecting up to 25 of women over 65. Decreased bone mineral density in the vertebral body is associated with an increased risk for spinal compression fractures. In primary care settings, 4 of patients who present with acute low back pain have compression fractures as the cause.14 Pain symptoms are worse with prolonged sitting or standing, and usually resolve over three to four months as compression fractures heal.6 African-American and Mexican-American women have only one fourth as many compression fractures as European-American women.5 Patients with compression fractures due to osteoporosis usually have no neurological complaints and do not suffer from neural compression. Plain radiographs document a loss of vertebral body height due to compression fractures. Laboratory tests are normal in primary osteoporosis, and any abnormalities should prompt a search for secondary causes of osteoporosis. The diagnosis of primary osteoporosis is...

Bone Mineral Density

Lower BMD, especially of the femoral neck, has been shown to be associated with an increased risk of stress fractures in the female athlete 56 . Although there are case-control studies that both support 57 and refute 49 this finding, Bennell and colleagues 53 were the first to examine this condition prospectively. They found that lower BMD in the lumbar spine and foot were significant predictors of later stress fracture development in female track and field athletes. Of note, an athlete with an apparently normal BMD (caused by the increased bone loading of sport) may be at an increased risk of stress fracture if she falls below the mean among female athletes. Also, as observed by dual x-ray absorptiometry scanning in athletic females, cancellous bone stress fractures correlate with early onset osteopenia much more than cortical bone stress fractures do 58 . This indicates the necessity of bone density evaluation in any young female with cancellous stress fracture. Menstrual...


Osteopenia in cancer survivors may be unrecognized in the absence of fractures unless evaluation is performed. Serum osteocalcin and urine pyridinoline crosslinks or N-telopeptide do not identify whether there is low bone mineral density. Identification requires performance of either a dual-energy x-ray absorptiometry (DEXA), which offers precise estimates of bone mineral area density (mg cm2) at multiple sites for the least amount of radiation exposure, or a quantitative computerized tomography (QCT), which measures true volumetric density (mg cm3) of trabecular or cortical bone at any skeletal site. T-score may be calculated in reference to normal young adults (age of peak bone mass is between 20-35 years) and Z-score in reference to age-matched normal individuals of the same gender. Results of DEXA must be adjusted for patient height and age.

Injury of the Hypothalamic Pituitary Axis in Patients with Cancer

Osteopenia GH deficiency is commonly believed to be the first hypothalamic-pituitary deficiency to emerge after injury to the HPA, followed by deficiencies of gonadotropin, ACTH and TSH 60,65 however, these deficiencies can occur in any order 11,21,35,54,67 . Although the most common neuroendocrinologic abnormality in survivors of childhood cancer is GH deficiency, hypothyroidism is at least as prevalent when sensitive testing methods are used 54 . The next most common alteration is in pubertal timing (precocious, rapid, delayed, or absent). ACTH deficiency, although less common than the other disorders, has more serious consequences if it is not detected. Osteopenia may result from hypothalamic-pituitary deficiency, particularly GH deficiency, hypothyroidism and hypogonadism. Hypothalamic injury resulting from tumor, surgery, or irradiation can result in unrelenting weight gain, termed hypothalamic obesity.

Low Calcium and Vitamin D Intake

Vitamin D is also essential to bone health, and its functions include stimulating calcium transport, osteoblastic stimulation, and decreasing parathyroid hormone. Recent studies have focused on the role of the vitamin D receptor allele in predicting bone density. More research is necessary to determine the clinical applications of its use in screening 86-88 .

In Vivo Function of the Oestrogen Receptors

The development of mice lacking the ERa (aERKO) or ERft (ftERKO) gene have proved to be valuable tools in evaluating the in vivo function of these receptors. The aERKO mice were generated in 1993, and the disruption of ERa expression not only caused infertility in both sexes, but also had profound effects on behaviour (Couse and Korach, 1999). Specifically, pre- and neonatal development of female reproductive organs such as uterus, ovary and mammary gland was almost normal, but maturation of these organs during and after puberty was severely impaired. The aERKO females also failed to display sexual receptivity when treated with the hormonal regime of oestrogen and progesterone that normally induces receptivity in wild-type mice. Surprisingly, adult aERKO males have significantly fewer epididymal sperm than heterozygous or wild-type males, caused by the disruption of spermatogenesis and degeneration of the seminiferous tubules, which becomes apparent 10 weeks after birth. Furthermore,...

Allowing Graves to Run Its Natural Course

Many with Graves' disease have mild symptoms and wonder whether they should refuse active therapy and allow Graves' disease to run its natural course, which might normally result in the thyroid gland burning out and failing on its own, leaving you hypothyroid anyway. This approach is commonly recommended for the small group of people who have such low degrees of thyrotoxicosis that ablative therapy with RAI, surgery, or risks of drug effects of antithyroid medications seem unnecessary. These people often do well with beta-blockers however, they must be carefully monitored since thyrotoxicosis may worsen without warning. Also, the risks of worsening of osteoporosis and chronic effects of excess thyroid hormone on the heart should be considered. For these reasons, post-menopausal women with brittle bones (see Chapter 14) and people with irregular heart rhythms (see Chapter 25) are appropriately directed toward RAI treatment.

Clinical Presentation of Dyskeratosis Congenita

DC is also known as Zinsser-Engman-Cole syndrome (Zinsser 1906, Engman 1926, Cole et al. 1930). Classically DC is characterized by the triad of abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. A variety of other noncutaneous abnormalities have also been reported since its first description (Table 5.1), including dental caries, tooth loss, esophageal webs, epiphora, short stature, developmental delay, hypogonadism, osteoporosis, pulmonary disease, premature grey hair, and hair loss (Trowbridge et al. 1977, Womer et al. 1983, Wiedemann et al. 1984, Zijlmans et al. 1997, Knight et al. 1998, Solder et al. 1998, Dokal 2000, Mason et al. 2005). osteoporosis

Treating Low or No PTH

Treating hypoparathyroidism means two things (1) taking enough vitamin D, and (2) taking enough oral calcium medication. The vitamin D is given in far higher doses than those recommended for the general population. The calcium pills are also given in higher dosages than just the regular supplements recommended for women with osteoporosis (see Chapter 14). Also, it is necessary to take the calcium pills at two or more times daily so that there is always some calcium in the intestine to be absorbed.

Bone Disease Any Link To Mitochondrial Toxicity

The prevalence and etiology of decreased bone mineral density (BMD) in HIV-infected patients are not completely known. The advent of decreased BMD in these patients seems to correlate with the introduction of HAART therapy. In a frequently cited study, Patton and colleagues describe a cohort of HIV-infected males with normal BMD that was stable over time before the HAART era (112). The reported prevalence of decreased BMD in HIV-infected adults has been in the range of 22 to 50 of adult patients with osteopenia and 3 to 21 with osteoporosis (113,114). As is true for patients with hyperlactatemia, most HIV-infected patients with decreased BMD are asymptomatic. Fragility fractures in these patients are limited to a few case reports in the literature (115,116), although recent case series of a large number of fragility fractures are a reason for heightened concern regarding the eventual development of these fractures as HIV-1-associated mortality falls (117). The etiology of decreased...

What Causes Bone Loss Anyway

Our bones are always regenerating (known as remodeling). This process helps to maintain a constant level of calcium in the blood, essential for a healthy heart, blood circulation, and blood clotting. About 99 percent of all the body's calcium is in the bones and teeth when blood calcium drops below a certain level, the body will take calcium from the bones to replenish it. But by the time we reach our late thirties, our bones lose calcium faster than it can be replaced. The pace of bone calcium loss speeds up for freshly postmenopausal women (three to seven years beyond menopause). One of the most influential factors on bone loss is estrogen it slows the loss of bone mass by directly affecting cells that make bone (osteoblasts) and cells that digest bone (osteo-clasts). In men, testosterone does the same thing, but unlike women, men never reach a particular age when their testes stop producing testosterone. If they did, they might be just as prone to osteoporosis as women.

How Much Calcium Do You Need

According to the National Institutes of Health Consensus Panel on Osteoporosis, premenopausal women require roughly 1,000 milligrams of calcium a day for peri-menopausal or postmenopausal women already on HRT or ERT, 1,000 milligrams and for peri- and postmenopausal women not taking estrogen, roughly 1,500 milligrams per day. For women who have already been diagnosed with osteoporosis, the Panel recommends 2,500 milligrams of calcium a day. Foods that are rich in calcium include all dairy products (an eight-ounce glass of milk contains 300 milligrams calcium), fish, shellfish, oysters, shrimp, sardines, salmon, soybeans, tofu, broccoli, and dark green vegetables (except spinach, which contains oxalic acid, preventing calcium absorption). It's crucial to determine how much calcium you're getting in your diet before you start any calcium supplements too much calcium can cause kidney stones in people who are at risk for them. In addition, not all supplements have been tested for...

Paula Cifuentes Henderson and Richard P Usatine

Osteoporosis is a major health concern affecting approximately 20 million people in the United States. It is responsible for more than 1.3 million fractures annually,1 with 15 billion in direct financial expenditures to treat these fractures.2 The clinical consequences of an osteo-porotic fracture include increased mortality, disability, and the need for long-term nursing care. After a hip fracture the mortality rate of patients 65 to 79 years old at 1 year is between 20 and 30 , and these rates worsen with increased age.3 Among those who survive, 50 won't be able to work without some type of assistance. After a collapsed osteoporotic vertebra, 30 of patients will experience chronic disabling back pain and spinal deformity.4,5 Osteoporotic fractures have a profound impact on quality of life, decreasing the physical, functional, and psychological performance secondary to pain, deformities, and inability to perform the activities of daily living (ADL)6. Osteoporosis is a disease...

Assessment and Diagnosis

Family history of osteoporosis (especially mother) Other risk factors such as age, gender, ethnicity, and slender body habitus can usually be observed without asking specific questions. The physical exam includes the measurement of height and weight, and the examination of the spine looking for any signs of deformity such as kyphosis, scoliosis, and limited range of motion. Screening for secondary forms of osteoporosis may be helpful. Assess the patient's risk of falling by asking about a history of falls and a decrease in visual acuity.10,11

Prevention and Treatment

Nonpharmacological therapy for prevention and treatment of osteoporosis includes adequate dietary intake of calcium and vitamin D, weight-bearing exercise, fall precautions, no smoking, and avoidance of excessive alcohol intake. These steps should be started early in life and continued through menopause because BMD peaks at about age 35 and then begins to decline with accelerated bone loss after menopause. According to the National Institutes of Health (NIH) Consensus Development Conference, the optimal recommended dose of elemental calcium is the amount that each person needs to maintain adult bone mass and minimize bone loss later in life (Table 8.3). The recommended dose for postmenopausal women < 65 years old who are on hormone replacement therapy (HRT) is 1000 mg day and 1500 mg day for all other postmenopausal women.27 Calcium supplements are advisable if diet cannot supply the recommended amount necessary. Calcium citrate should be taken between meals while calcium carbonate...

Various Transporter Defects Hartnups Disease

Male infants usually present at 2 to 3 months with developmental arrest and regression, hypotonia, seizures, and failure to thrive. Seizures are an early presentation, are frequent, and are multifocal myoclonic jerks that are often stimulus-precipitated. Recurrent hypothermia and infections occur. The near-pathognomonic clinical sign is scarce, colorless, wiry, friable hair on scalp and eyebrows and, under the microscope, the characteristic appearance of pili torti (twisted hair shaft). Secondary microcephaly occurs later. A mild Menkes' disease variant occurs, with later onset and milder neurological findings. The occipital horn syndrome, another variant, has few mental or neurological signs but calcified occipital horns, changes in clavicles and long bones, and sometimes chronic diarrhea and arterial changes. The differential diagnosis includes any early infantile progressive encephalopathy presenting with seizures, such as storage disease (Tay-Sachs disease, Sandhoff's disease,...

Other Antiobesity Pills

Another antiobesity drug, sibutramine, was approved for use in 2001. Sibutramine is meant for people whose body mass index (BMI) registers at 27 or higher. But if you're on thyroid hormone, as well as medications for depression, seizures, glaucoma, osteoporosis, gallbladder disease, liver disease, heart disease or stroke prevention, kidney disease, migraines, or Parkinson's disease, you should discuss whether sibutramine is appropriate.

Treating Hypothyroidism in Older Persons

The risk of thyrotoxicosis from excessive dosages of thyroid hormone in an older person with either heart problems and or osteoporosis means that thyroid hormone dosing is often a start low, go very slow approach. This is the advice that internists and family physicians are given however, experienced endocrinologists are often able to better choose appropriate dosages that are not excessive without having to delay treatment by starting too low. Older people also require less thyroid hormone than younger people, which is why starting doses of thyroid hormone are advised to be conservative. It is in this group, especially, that T3 in combination with T4 has not been properly evaluated and could have adverse effects (see Chapter 10). Similarly, natural thyroid hormone or thyroid extract (see Chapters 3, 10, and 19) is not recommended in this group.

Michael L Tuggy and Cora Collette Breuner

Family physicians routinely treat many athletic injuries in their clinical practice. The benefits of long-term exercise in the prevention of common illnesses such as cardiovascular disease, osteoporosis, and falls in the elderly are well established. With the increased interest in fitness in the general population, the number of people resuming more active exercise as they age is increasing. Injuries sustained in childhood or adolescence may have long-term effects that can hamper later attempts at physical activity.1 For all ages of patients, proper training and prevention can lead to lifelong participation in athletic activities.

The Hyperthyroid Diet

You might lose weight and experience hyperdefecation (frequent bowel movements). While thyrotoxic, increase your calcium intake by having more dairy products. This is more important for women who are at risk for osteoporosis (see Chapter 14), which can be aggravated by thyrotoxicosis. This will also help to keep your weight up. Peanut butter, mayonnaise, and animal fat can help as well. To reduce diarrhea, cut down on fruit juices and fresh fruits. Peanut butter is also good for binding. Sometimes, thyro-toxic people will develop sudden lactose intolerance. This can lead to gas and other unpleasantness. Eliminate all milk products in this case, and take a calcium supplement while getting your fat from the other foods mentioned previously.

Basis for Sports Nutrition Interest

Whether it is by affecting the formation and structure of collagen, the binding of macromole-cules to cell receptor sites, or the utilization or absorption of some mineral affecting bone formation, there is evidence that increased silicon consumption is beneficial to bone health. Jugdaohsingh et al.181 reported that in a cross-sectional, population-based study (2847 participants), dietary silicon correlated positively and significantly with bone mineral density at all hip sites in men and premeno-pausal women, which suggests that increased silicon intake is associated with increased cortical bone mineral density in these populations.

Risk Based Healthcare Definition and Rationale

Radiation therapy (breast, thyroid and skin), altered bone metabolism and osteoporosis, obesity-related health problems (dyslipidemia, hypertension, diabetes mellitus, cardiovascular disease), liver failure secondary to chronic hepatitis C following blood transfusion and endocrine dysfunction following chest mantle or cranial radiotherapy. Primary, secondary and tertiary prevention, including tobacco avoidance cessation, physical activity, low-fat diet and adequate calcium intake, can modify risk. Longitudinal care addressing other late effects, such as infertility, musculoskeletal problems, cognitive dysfunction and psychosocial issues, may also improve survivors' health outcomes and quality of life.

Basis for Sports Nutrition Interest 1 Insulinomimetic Actions

One of the first vanadium-deprivation signs reported for chicks was adverse effects on bone devel-opment.206 Histological examination of the tibias from vanadium-deprived chicks revealed severe disorganization of the cells of the epiphysis. The cells appeared compressed and their nuclei flattened. These abnormalities apparently were the reason that vanadium-deprived chicks had a shortened, thickened leg structure. Bone abnormalities were also found in vanadium-deprived goats.205 Compared with goats fed a 0.5-2-mg V kg diet, goats fed less than 10 g kg diet exhibited pain in the extremities, swollen forefoot tarsal joints and skeletal deformations in the forelegs. These changes in bone suggest that vanadium may have a role that affects bone or connective tissue metabolism. This suggestion is supported by the finding that vanadium stimulated the mineralization of bones and teeth213 and the repair of bones.214 Orthovanadate stimulates bone cell proliferation and collagen synthesis in...

Indications For Surgery

Surgery is also warranted when complications or unacceptable side effects related to specific agents occur and alternative medical therapies are not appropriate or are ineffective. Corticosteroid-induced complications are commonly encountered by Crohn's disease patients and include cushingoid features, weight gain, hypertension, diabetes, myopathy, osteopenia, compression fractures, aseptic necrosis of the femoral head, psychoses, and cataracts.

Pierre Mac Neil and Lawrence Rosenberg Introduction

In the last century, and especially over the past 10 years, biomedical science has progressed rapidly. Selected cancers can be treated, organs can be transplanted, and joints can be replaced. In addition, drugs that can lower the risk of myocardial infarction and prevent fractures caused by osteoporosis, are now commonly prescribed. The treatment options are endless, and everyday brings a new technology that promises better health. However, all new and existing treatments come at a price and the question of what is expensive vs. what is affordable, is one which must be constantly addressed. One thing, however, is certain. After 30 years of double digit growth in health care budgets, it is clear that the amount of resources that can be devoted to health care is finite. With this realization, the necessity of developing tools to assist in making tough choices between interventions has emerged.

Animal Species for the Model

To answer all preclinical questions the model should manifest the human disease process under evaluation and possess immunologic characteristics similar enough to humans to allow an estimation of autoimmune and allogenic rejection. Models for many human endocrine diseases have been established in mice, including type 1 diabetes mellitus (DM) (64-67), type 2 DM, thyroiditis (68), and osteoporosis (Table 2) (69,70). But nonhuman primates, who share similar immune systems to humans, do not spontaneously develop all of the human diseases of interest, in particular type 1 DM. Because there is not a single animal model that is ideally suited to answer all preclinical questions, careful integration of the results collected from multiple animal models into a coherent framework may be the only viable alternative. Osteopenia osteoporosis

Should you arch your back

Neck And Shoulder Muscles

* For people who are not fully grown or people experiencing osteoporosis, extending the lumbar spine may lead to spondylolysis because of fractures in the vertebral arch. This fracture in the posterior anchoring system of the vertebra may allow the vertebra to slide forward and seriously compress the neural elements (which leads to sciatica).

Principles Of Diagnosis

Femoral shaft fractures are difficult to diagnose because of the vague nature of pain, poor localization of tenderness, and few reliable physical examination findings 1,6,10,19 . Other disorders must be considered before proceeding with treatment for a stress fracture of the femur. Vascular, metabolic, inflammatory, infectious, and neoplastic conditions as well as other overuse injuries should be considered in the differential diagnosis. In the proximal femur, these conditions include avascular necrosis, infection, transient osteoporosis, bursitis, tendonitis, synovitis, synovial herniation, muscle or tendon injury, and neoplasm. Femoral shaft pain may be the result of muscle strain, contusion, infection, or neoplasm. Distal femoral pain may be related to internal knee derangement, femoral condyle avascular necrosis, infection, tendon or ligament injury, or neoplasm. In elderly athletes, it is particularly important to con

Mitochondrial DNA Mutations and Aging

The introduced mutation was designed to create a defect in the proofreading function of Polg, leading to the progressive, random accumulation of mtDNA mutations during the course of mitochondrial biogenesis. As the proofreading in the knockin mice is efficiently prevented, these mice develop an mtDNA mutator phenotype (mtDNA mutator mice) with a three to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA molecules 75 . In contrast to the mitochondrial theory of aging, we have shown that the levels of somatic mtDNA mutations accumulate at a higher rate during the time of development from oocytes to early embryonic life of mtDNA mutator mice, than during the rest of their life when mutations accumulate in rather linear fashion 76 . The mtDNA mutator mice display a completely normal phenotype at birth and in early adolescence but subsequently acquire many features of premature aging. The increase in somatic...

Progressive Diseases of Infancy and Childhood

Osteoporosis is a common late complication, and half of the patients will show some evidence of it by 20 years of age. It is more severe and appears earlier in pyridoxine-nonresponsive patients. Biconcave vertebrae are seen. The maturation of the skeleton is abnormal and leads to lengthening of the long bones (dolichostenomelia), which accounts for the marfanoid appearance of patients.

Clinical picture of hypogonadism

After puberty, the clinical picture may vary considerably according to the time elapsed since puberty and the degree of the androgen deficiency. Body proportions, size of penis, and pitch of voice do not change. Body and facial hair may decrease. The main clinical signs are reduced sexual desire and potency, and infertility. Size and consistency of testes vary from normal to significantly reduced. Long-term androgen deficiency usually causes atrophy of muscle mass, osteoporosis, loss of strength and energy, normochromic and normocytic anemia, fatigue, and mood disturbances.

Mineral Exchange In Teeth

Altkorn D, Vokes T Treatment of postmenopausal osteoporosis. JAMA 285 1415, 2001. Delmas PD Treatment of postmenopausal osteoporosis. Lancet 359 2018, 2002. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA 285 785, 2001.

Pathophysiology of DHEA deficiency

Low DHEA levels have also been described in a variety of non-endocrine medical conditions. The age-related decline in circulating DHEA levels may correlate with many age-related phenomena such as diabetes and states of insulin resistance, hypertension, atherosclerosis, coronary artery disease, decreased bone mineral density, cancer, and dementia 287-291 . Low levels of DHEA have also been described in correlation with various conditions unrelated to aging, including obesity, depression, and other mood disorders, eating disorders, autoimmune disorders, immune deficiency states, and chronic stress states 287-289,292,293 . In the Massachusetts Male Aging Study (MMAS) DHEA-S was the only hormone which showed a strong (negative) correlation with the prevalence of ED among 17 investigated hormones, including T and estradiol 294 .

Bone and Connective Tissue

Radiation therapy has an effect on wound healing that may be critical for those who require a surgical procedure in the irradiated region 13 . RT may also affect the connective tissues and bone, leading to fibrosis and osteoradionecrosis. In the Fromm series, two patients developed temporomandibular joint fibrosis with limitation of jaw motion 23 . Osteo-radionecrosis has been well described in the adult head and neck literature however, little has been written on its incidence in the pediatric population. Osteoradionecrosis usually develops in the mandible and its risk is directly correlated with total radiation dose, fractionation dose, tumor size and bony involvement by the tumor. The risk is also increased in dentulous patients and even more so if these patients receive postirradiation extraction, compared with pre-irradiation extraction. Amifostine may confer radioprotection of craniofacial bone growth inhibition. Pretreatment with amifostine, 20 minutes before 35 Gy RT, resulted...

Mechanism of action and conversions

About 80 of DHT is produced in peripheral tissues and the remaining 20 is secreted directly by the testis. Furthermore, approximately 30-40 g of estradiol is produced by the adult male, mainly in peripheral tissues, such as adipose tissue, bone, prostate, and brain. Insight into the biologic actions of estradiol in the male is rather recent. Estrogens have an important effect on the final phases of skeletal maturation and bone mineralization in puberty. In addition, from some studies in elderly men it appears that estrogen levels show a higher correlation with bone mineral density (BMD) than androgen levels 3 . Impaired estrogen action in men leads to dyslipidemia and to endothelial dysfunction. Observation in men with aromatase deficiency is linked to a complex dysmetabolic syndrome characterized by insulin resistance, diabetes mellitus type 2, acanthosis nigricans, steatosis hepatis, and signs of precocious atherogenesis, remedied by estrogen administration. Estrogen...

The Protein Defective in Werner Syndrome WRN

Werner syndrome (WS) is a homozygous recessive disease characterized by early onset of normal ageing including wrinkling of skin, greying of hair, cataracts, diabetes and osteoporosis. Neoplasms, particularly sarcomas, are observed at higher prevalence in WS patients than in normal individuals of the same age. The symptoms of WS begin to appear near puberty, and most patients die before reaching age 50. Because the clinical features of WS are similar to symptoms of ageing in normal individuals of more advanced age, WS is considered to be a segmental progeria. One of the motivations to study WS is its resemblance to ageing thus, knowledge of the mechanism and molecular basis of WS might give insight into normal ageing and ageing-associated diseases such as cancer.

Definition and Clinical Descriptions

Most of the physiological and metabolic changes in AN are secondary to the starvation state or purging behavior. These changes revert to normal with nutritional rehabilitation and the cessation of purging behavior. Hypokalemic alkalosis occurs with purging. These patients may have hy-pokalemia and physical symptoms of weakness, lethargy, and cardiac arrhythmias, which may result in sudden cardiac arrest. Persistent vomiting causes severe erosion of the enamel of teeth, with consequent loss of teeth, and produces parotid gland enlargement (Halmi, 1999). Chronic food restriction produces osteoporosis and fractures.

HRT Menopause and Thyroid Disease

National Heart, Lung, and Blood Institute, part of a huge research program called the Women's Health Initiative (WHI), suggested that HRT should not be recommended for long-term use in fact, the results were so alarming, the study was halted before its completion date. It was found that Prempro, a combination of estrogen and progestin, which was a standard issue HRT formulation for postmenopausal women, increased the risk of invasive breast cancer, heart disease, stroke, and pulmonary embolisms (blood clots). The study participants were informed in a letter that they should stop taking their pills. However, Prempro did reduce the incidence of bone fractures from osteoporosis and colon cancer.

Prevention Strategies

A critical component to prevention is health counseling for females at risk. For females treated during the prepubertal period, parents should be counseled regarding the risk of primary ovarian failure. Normal gonadal development should be reviewed with recommendations for monitoring of growth and development. Reproductive counseling should be made cautiously and preferably, in conjunction with a specialist in reproductive endocrinology. The effects on the female gonadal system from radiotherapy and chemotherapy may demonstrate significant inter-individual variation, even with identical exposures at identical ages. Post-pubertal females who have normal menstrual function should be counseled about appropriate contraception should they currently not wish to conceive a child, and they should also be made aware of their potential risk for premature menopause. Not inconsequential for young adults is the impact of ovarian failure or impending failure in sexual drive or libido, an effect...

The Female Athlete Triad

The female athlete triad refers to an interrelated problem consisting of disordered eating, amenorrhea, and osteoporosis. Hoch and colleagues 93 have also found that amenorrheic athletes have reduced brachial artery endothelium-dependent flow-mediated vasodilation compared with oligomenorrheic and eumenorrheic athletes. Furthermore, in a 2-year follow-up study, the original amenorrheic athletes were found to have a significant improvement in BMD with different combinations of estrogen and progesterone or the return of menses naturally. The female athlete triad is a potentially lethal combination of medical disorders reported in some female athletes 4,42 . The athletes at greatest risk appear to be those who feel significant pressure to excel in sports for which leanness and a low body weight are considered advantageous, such Abnormal eating patterns may lead to athletic-associated amenorrhea. Athletic amenorrhea is a complex multifactorial condition with serious associated...

Anatomy And Biomechanics

The fibula plays a secondary role in weight bearing. The load borne by the fibula varies from 2.3 to 10.4 of the total load applied and depends on ankle position and loading orientation 17 . Muscular forces have been postulated to play a role in the occurrence of fibular fractures 8,18 . Strong contractions of the ankle plantar flexors in runners are believed to approximate the fibula to the tibia, with resultant stress concentration at the more proximal distal site 8 . As for the distal fibular stress fractures, which occur predominantly through cancellous bone, osteoporosis is believed to play a role because these fractures are more common in older females who are more prone to bone mineral density changes 5 . Recurrent forces of eversion, opposed by the stabilizing force of the syndesmotic ligaments, create a valgus moment at the ankle with stress concentration at the level of the ankle joint mortise 13 . Lateral malleolar insufficiency fractures in patients who have...

Candidates for androgen therapy

It is generally accepted in clinical practice that any male with any form of classical hypogonadism and inadequately low T for his age will require androgen therapy if hypogonadism occurred before the age of 50 213 . Even in men who have proceeded normally through puberty, and who experience no or only minor symptoms (e.g. fatigue, reduced libido), T therapy may be recommended, to prevent long-term sequelae such as osteoporosis 1 . Conversely, there is much debate concerning the validity of this therapy in men with sexual dysfunction and low normal T levels, those with chronic illness and low T, and those with LOH, even if the decline in BT may be partially responsible for the frailty syndrome seen in the aging male 214 . The recommendation common to

Organ Damage Induced by Cytotoxic Therapy

Radiotherapy and chemotherapy each may cause transitory or permanent effects on hormonal function, reproductive capacity and sexual function. Primary ovarian failure, impaired development of secondary sexual characteristics, menstrual irregularities, including oligomenorrhea and amenorrhea, or premature menopause may occur. The menopausal state, when it occurs prematurely, is associated with the same physical symptoms as are seen with normal aging,including hot flashes,loss oflibido and osteoporosis 2,3 . Such effects are not simply physically bothersome to survivors, but adversely impact their quality of life 4 . The specific effects are dependent on the ovarian dose of radiation and the chemotherapeutic agents and their doses. They also depend on the developmental status of the patient at the age of treatment.

The mTerc Wrn Compound Mutant Mouse as a Model of Human Werner Syndrome

Interestingly, despite the wide-ranging activities of the WRN helicase in human cells, Wrn null mice do not exhibit any cellular or clinical phenotypes characteristic of human WS (Lombard et al. 2000). The observations that WRN is required for telomere maintenance, and that laboratory mice normally possess very long telom-eres, suggest that manifestation of premature aging phenotypes in Wrn-null mice may require the presence of critically short telomeres. This hypothesis has since received genetic support from studies of mice lacking both telomerase and Wrn (Chang et al. 2004, Du et al. 2004). Strikingly, these late-generation mTerc ' Wrn ' mice display clinical symptoms resembling human WS, including early onset of age-related disorders such as impaired wound repair, osteoporosis and skeletal fractures, hypogonadism, cataract formation, type II diabetes, and premature death. These mice also exhibit an elevated incidence of mesenchymal cancers compared with control mice (Chang et al....

Inhibitors of Bone Resorption

Hormone Replacement Therapy (HRT) In the PEPI trial, HRT increased BMD at the hip by 1.7 and at the spine by 3.5 to 5.0 over a 3-year period compared to placebo. HRT inhibits bone loss for the duration of the therapy, which recurs once therapy is discontinued. In premenopausal women with osteoporosis secondary to hypoestrogenic stages, early intervention with estrogen to achieve return of menses, is critical since bone loss may be irreversible. Selective Estrogen Receptor Modulators (SERMs) SERMs are an important alternative for women with contraindications or intolerance to estrogen therapy. Tamoxifen and raloxifene were FDA approved in 2000 for treatment of postmenopausal osteoporosis. The main goal is to maximize the beneficial estrogenic effect in bone and minimize the effect on the breast and endometrium.

Stimulators of Bone Formation

Density at the lumbar spine and does not reduce the number of vertebral fractures. Increasing the dose of fluoride actually increased the risk of nonvertebral fractures and gastrointestinal side effects.42 It is not approved by the FDA for osteoporosis prevention and treatment.

Intravenous Pamidronate

Stewart and colleagues 46 reported on the use of intravenous pamidronate on five symptomatic collegiate athletes who had tibial stress fractures. Pamidro-nate is a second-generation bisphosphonate that is currently used in the treatment of osteoporosis, hypercalcemia, and metastatic bone disease. It is thought to affect osteoclastic activity by binding to calcium phosphate crystals. With decreased osteoclastic activity, the osteoblasts may catch up, allowing the bone to heal. A 30-mg test dose was given intravenously over 2 hours, followed by four additional treatments at weekly intervals in 60-mg or 90-mg amounts. With the initial treatment, four of five subjects were able to continue training without symptoms within 72 hours. The fifth patient missed 3 weeks of training. At a minimum of 49 months of follow-up, all athletes remained asymptomatic. These investigators believe that the treatment is promising and plan to do a prospective study.

Michael C Koester Md Atc Kurt P Spindler MD

This article discusses the current understanding of the potential role for bisphosphonates, parathyroid hormone (PTH), and vitamin D supplementation in the treatment of sports-related fractures. The available evidence regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and their effects on fracture healing are also reviewed. Discussion focuses on the applicability of these findings to the sports medicine population the potential role of pharmacologic agents for implant fixation and osteoporosis treatment are not discussed.

Differentiation Studies

SYSTEMIC DELIVERY Another potential application for MSCs is the systemic introduction of osteogenic cells to counteract age-related osteoporosis or as a potential cure for osteogenesis imperfecta (Caplan and Bruder, 2001). To effectively treat these diseases, it is necessary to devise a method for the systemic introduction of MSCs. The literature on the subject of circulating MSCs contains conflicting results. Early studies

Aastrom Biosciences

Of adult stem cells from bone marrow and umbilical cord blood. It also provides a kit for isolating stem cells, called the AstromReplicell System, which provides standardized methods and reagents for directed differentiation. The company's cells and isolation system are being used in clinical trials to treat breast cancer, leukemia, osteoporosis, and lymphoma.

Future Research Directions or Needs

Research is needed to determine the validity of having supplements containing high amounts of vanadium in the marketplace. This research should definitively establish the toxicity threshold for vanadium and determine whether long-term high consumption of vanadium could lead to pathological disorders such as hypertension.236,237 Studies are needed to determine whether supra nutritional, but non-toxic, intakes of vanadium enhance athletic performance or bone health. Definition of a biochemical function for vanadium at physiological intakes is needed before this element can be considered essential. Definition of an essential function would help differentiate between nutritional and pharmacological actions of vanadium and could be used to determine whether low dietary intakes of vanadium are of practical nutrition concern for the general public in addition to athletes. It is obvious that it is premature to recommend vanadium supplements for enhancing strength, muscle mass and athletic...

Utilization and Validation of Animal Models

Comprehensive monitoring of bone mineral density and turnover in flight crews was instituted in the past. However, despite success in obtaining sequential bone mass measurements and specimens for turnover measurements, the results of these studies are fragmentary and not generally available. The current Astronaut Medical Evaluation Requirements Document (AMERD) for missions exceeding 30 days mandates dual energy x-ray absorptiometry (DXA) assessment of body composition and bone mineral density one month prior to, and about one week after, completing the mission. The Strategy report clearly recommended the collection and maintenance of a database adequate to document and characterize the nature and distribution of bone loss during spaceflight missions. However, it does not

Winnipeg Jets Standings

Form of p53 display premature ageing phenotypes such as reduced longevity, osteoporosis, generalized organ atrophy, and diminished stress tolerance (Tyner et al. 2002). Moreover, it has been shown that hypermorphic levels of p53 in these mice affect hematopoietic stem cell (HSC) number, proliferation, and _ functionality with age, whereas deletion of one copy of p53 increased HSC proliferation during mouse ageing (Dumble et al. 2007). In contrast, telomere dysfunctional mice carrying an extra copy of wild-type p53 gene under its natural promoter (total three copies of p53) did not show an increase in tissue atrophy or a shortening in life span (Garcia-Cao et al. 2006). These results were surprising since telomere dysfunctional mice carrying an extra copy of p53 are expected to have a 1.5-fold increase in p53 gene dosage when compared to telomere dysfunctional mice with only two copies of p53. Notably, the in vivo load of telomere-derived chromosomal damage was significantly decreased...

Nutritional Habits

Proper nutrition is necessary for optimal bone health in the young athlete. In a retrospective study, Myburgh and colleagues 29 reported a lower intake of calcium in athletes who had stress fractures. Disordered eating patterns must always be considered and corrected whenever a stress fracture is diagnosed. This is especially true in the female athlete who has multiple stress fractures. In such circumstances, the athlete must be evaluated for the female athletic triad 30 , consisting of disordered eating, amenorrhea, and osteoporosis. Severe eating disorders are considered medical emergencies and often require a multidisci-plinary approach including nutritional and psychologic counseling.


Interestingly, there have been no grades 2, 3, or 4 serum creatinine elevations associated with tenofovir DF administration in phase II or phase III clinical trials (23). These findings are particularly significant given the high rate of proximal renal tubular dysfunction described with the structurally similar compound, adefovir dipivoxil. The frequency of grade 3 or 4 serum hypophosphatemia in clinical trials was low ( 1 ) and reversible with discontinuation of treatment (23). In addition, bone mineral density testing was performed in a small proportion of subjects participating in the phase II study (GS-98-902), and no clinically significant decrease in bone mineral density from baseline was demonstrated in patients receiving tenofovir DF through 48 wk (21). In a combined analysis of the phase II and phase III studies (GS-98-902 and GS-99-907), no increase in bone fracture rate was seen with tenofovir DF treatment (687 subjects with 778 patient-years of exposure fracture rate 1.7...

Human Studies

Of a dual energy X-ray system for bone mineral density and diagnostic radiography. At JSC, a project has been initiated to estimate the calcium kinetics and bone turnover on spaceflight missions. This project represents a continuation of work done in association with the Mir program.


The tolerable upper intake level should not exceed 2800 g retinol for adolescents (14-18 years) and 3000 g retinol for all adults. High levels of vitamin A supplementation will not improve athletic condition, and may cause direct toxicity symptoms, including bone pain, headaches or peeling of skin (desquamation). Even a relatively mild oversupply of vitamin A might induce teratogenic effects in fetal development and increase the risk of osteoporosis in older men and women. Estimates of vitamin A dietary intake among athletes in developed countries indicate adequate nutrition, but suffer from methodological problems of inaccurate reporting by subjects, changing and confusing rules of vitamin A activity conversion for carotenoids in plant based foods and the habit of reporting vitamin A from all sources together, without specifying the proportion from animal sources, fortified foods and supplements on one side, and provitamin A carotenoids on the other. The dietary interview...


Other vitamin K-dependent proteins exist. These include osteocalcin, which is used in the formation of bone. These proteins (those found within osteocalcin) are also found in cartilage, dentin and bone. These proteins are partially dependent on vitamin D. Thus, vitamin D and vitamin K have vitamin-vitamin interactions that are important for bone health and blood clot formation. Young athletes who are still in the formative years or peak years for bone density may be of prime concern to a sports nutritionist for their dietary intake of both vitamins D and K.


Athletes are at risk for developing either fatigue or insufficiency fractures. Extrinsic risk factors include training schedule, diet, playing surfaces, and equipment such as footwear. Intrinsic risk factors include age, gender, lower-extremity alignment (leg length inequality, coxa vara, or cavus foot), low bone mass, menstrual cycles, and metabolic disorders 3,27,34,35 . Generally, training errors are the most frequently encountered causes of stress fractures 1,10 . Athletes suddenly either increase the intensity of a routine workout or start a new exercise at a level that is beyond the normal physiologic response of bone. Insufficiency fractures in athletes are most commonly related to a metabolic problem related to diet or hormonal imbalance. A daily diet needs to provide sufficient calories to support certain levels of physical activity in athletes. Daily recommended doses of calcium and vitamin D also should be taken to maintain adequate bone density. Female athletes deserve...

Genetic Issues

The prevalence of osteoporosis varies by sex, ethnicity, and race.12 Decreased bone density is more common in women of Northern European or Asian descent. Women and men experience age-related decrease in bone mass density starting at midlife, but women experience more rapid bone loss after the menopause.13 Genetic syndromes like Turner's (45,X0) syndrome patients have streak ovaries and decreased estrogen production leading to the early development of osteoporosis.14


Excessive use of alcohol depresses osteoblastic function and increases the risk of osteoporosis. Physical activity early in life contributes to higher peak bone mass and reduces the risk of falls by approximately 25 .16 Good nutrition with a balanced diet is necessary for the development of healthy bones. Calcium and vitamin D are required for the prevention and treatment of osteoporosis. There are data to support recommendations (found later in the chapter) for specific dietary calcium intakes at various stages in life.17,18 Patients at high risk also include those who pursue thinness excessively, have a history of an eating dis-order,19 restrict their intake of dairy products, don't consume enough vegetables and fruits, and have a high intake of low-calcium high-phosphorus beverages like sodas. These beverages have a negative effect on calcium balance. If the history and physical exam suggests secondary causes of osteoporosis, the physician should consider tests such as...


17 -Estradiol is the main estrogen synthesized and secreted by normal female ovaries. Its oxidized analog, estrone, is secreted to a significantly lesser degree by premenopausal ovaries. The hormonal effect of estrogens on target tissues is based on a complex mechanism that includes their reaction with specific estrogenic cytoplasmic receptors. After binding with these receptors, a conformational change occurs, which results in the estrogen-receptor complex penetrating into the nucleus, where it disassociates and returns to its native condition. Estrogens are used for insufficient ovary function. Estrogen replacement therapy is used in agonadal, menopausal, hypothalamic, and amenorrheal conditions (i.e. in cases of primary hypogonadism and hormone therapy in postmenopausal women). Estrogens are also recommended for other clinical endocrine diseases if hypoestrogenism has been established. Estrogens are most widely used in combination with progestins in a number of oral contraceptive...

Alendronate Fosamax

Alendronate was approved by the FDA in 1995 for treatment of post-menopausal osteoporosis. It reduces the risk of vertebral fractures by 30 to 50 and increases the BMD at the spine and hip.35 Alendronate also reduces the risk of fractures in men and women with osteoporosis secondary to the chronic use of steroids.36 The recommended starting dose for postmenopausal osteoporosis prevention is 5 mg day with a maintenance dose of 10 mg day. The most common side effect is esophageal irritation secondary to reflux. Therefore, the patient should take alendronate with a full glass of water without food and remain upright for at least 30 minutes to avoid reflux. Another available regimen is 70 mg once a week. This weekly dose was demonstrated to be as effective with fewer gastrointestinal

Risedronate Actonel

Risedronate is a newer biphosphonate approved in 2000 by the FDA for treatment of postmenopausal osteoporosis. While the indications are the same as alendronate, it has fewer gastrointestinal side effects. Both agents cost over 50 a month. In a randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline, risedronate decreased the relative incidence of new vertebral fractures by 41 over 3 years. The absolute risk reduction was from 16.3 to 11.3 . The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39 (5.2 vs 8.4 ). The overall safety profile of rise-dronate, including gastrointestinal safety, was similar to that of placebo. The most effective dose was 5 mg day.39 Calcitonin is helpful when treating painful osteoporosis due to its significant analgesic effect. This hormone inhibits bone resorption by acting directly on the osteoclasts. The PROOF study is...


Fractures of the hip, vertebrae, and wrists from osteoporosis cause significant decreases in the quality of life for many older individuals. The complications of hip fractures can also lead to death. Better methods for prevention, early detection, and treatment now exist. Healthy lifestyles, including no smoking, exercise, good diet, and calcium intake, can help to prevent osteoporosis. By assessing family history, ethnicity, body type, and other risk factors, physicians can target prevention and screening efforts to patients at highest risk for osteoporosis. Patients at higher risk should probably be screened using a DEXA scan. Pharmacological therapies such as hormone replacement, calcium, vitamin D, bisphosphonates, SERMs, and calcitonin can help prevent BMD loss and may reduce the risk of fractures. Currently, the data for fracture prevention are stronger for the bisphosponates than for hormonal therapy. Every family physician should feel comfortable screening for, preventing, and...

Risk Factors

Various intrinsic and extrinsic risk factors have been described for stress fractures. Fatigue fractures occur when normal bone is stressed at a rate that exceeds the ability of the bone to remodel to a stronger state and adapt to greater force and cycles. Insufficiency fractures occur when abnormal bone is routinely stressed under conditions of, for example, osteoporosis, Paget s disease, and rickets. The majority of stress fractures about the ankle are fatigue fractures.

Diagnostic Imaging

Plain radiographs are useful in the initial evaluation of an athlete in whom a stress fracture is suspected. In more advanced or established cases, cortical or medullary fracture lines, regional osteopenia, sclerosis, and callus formation may be noted. Unfortunately, radiographs are initially negative in up to 70 of stress fractures and may not show evidence of injury for 2 to 4 weeks after symptoms begin 28 . In two of the largest series of medial malleolar stress fractures, Shelbourne and colleagues 15 and Orava and colleagues 20 have noted only two of six and three of eight patients, respectively, who had positive initial radiographs. Other authors have reported positive initial radiographs in less than half of their patients who had a suspected medial malleolus stress fracture 22,27 . A characteristic cystic lesion associated with medial malleolar stress fractures caused by microfracture and bone resorption has been described 21,27 .

Hip Fractures

And fracture of the hip in those 65 years and older (see Reference 56, Chapter 24). Although hip fractures are a common malady of the elderly, anyone subjected to sufficient forces to the hip can be affected. The overall incidence approximates 250,000 hip fractures per year in the United States. In 1996 there were 340,000 hospital admissions for hip fractures in the United States.1 Hip fractures are associated with more deaths, disability, and medical cost than all other osteoporotic fractures combined. Osteoporosis is the biggest risk factor for hip fracture. Table 3.1 outlines the major risk factors for osteoporotic hip fracture. tensile trabeculae, and wider trochanteric region) on plain radiographs were as predictive of risk for hip fracture as bone mineral density determinations.4 Dexa scanning has become an important tool in screening for osteoporosis. The best treatment for osteoporosis is prevention. Preventive measures include hormone replacement therapy, exercise,...

DHEA therapy

Other proposed uses for DHEA therapy In addition to theoretical anti-aging effects and potentially beneficial metabolic effects of DHEA supplementation, the effects of exogenous DHEA administration have been studied in other conditions. Beneficial effects on mood have been observed while using DHEA as treatment for depression and dysthymia 314,315 . DHEA supplementation in Alzheimer disease has been shown to cause only minor and transient improvements in cognitive performance 316 . In terms of bone health, the beneficial effects of DHEA supplementation are felt to be minor and limited to women 314 . DHEA supplementation has been shown to reduce the frequency of flares, and to decrease steroid dose requirements, in women with systemic lupus erythematosus 314,316 . DHEA has also been studied as a potential chemopreventive, anticarcinogenic agent 317 . The potential for immunoregulatory effects of DHEA has been demonstrated by the presence of specific binding found in murine T cells 318...


Men with aromatase deficiency or inactive estrogen receptor a develop severe osteoporosis. Most of the effects of T on bone depend on its aromatization into estradiol. Estradiol is also supposed to be the main active metabolite of T concerning its effects on the brain, though no significant sexual dysfunction was observed in men affected by congenital estrogen deficiency 258-260 . However in two men with aro-matase deficiency, Carani etal. observed a synergistic effect of estradiol and T on sexual behavior

Future therapies

Induction of gynecomastia, infertility, and overstimulation of erythropoiesis. On the other hand, use of SARMs for selected indications provides the rationale for developing molecules with distinct tissue specificity. For example, if the target is bone growth in elderly men with osteopenia or osteoporosis, but with no overt signs of hypogonadism, a more anabolic SARM with clear effects on bone and muscle, but lesser activity on prostate or other sex accessory tissues, would be more desirable. * Selected indications may include glucocorticoid-induced osteoporosis, androgen replacement in eldery men, HIV-wasting, cancer cachexia, certain anemias, muscular dystrophies, and male contraception. DHT, dihydrotestosterone. With permission of Negro-Villar A. J Clin Endocrin Metab 1999 84 3459-3462 224 . * Selected indications may include glucocorticoid-induced osteoporosis, androgen replacement in eldery men, HIV-wasting, cancer cachexia, certain anemias, muscular dystrophies, and male...

Skeletal System

The extreme result of this imbalance is osteoporosis, a condition in which the bone loses so much density that it becomes porous and brittle. Genes, gender, diet, hormones, age, and activity all contribute to determining the severity of this condition. Osteoporosis is most typical in post-menopausal women, who have low blood levels of the hormones estrogen and progesterone. Men can get osteoporosis, too, but their testosterone supports building greater bone mass. Though their risk is less than women's, men can get osteoporosis as their testosterone levels decline with age. Several hormones and other drugs are successful in slowing osteoporosis, but exercise and a high intake of calcium can make it less likely to occur. The teenage years, marked by rapid body growth, are critical for producing bone mass. Stimulated by thyroid hormones, the osteoblasts use all of the calcium and protein provided by the osteoclasts, plus much of that in the diet. Dietary calcium is particularly valuable...


Over the past decade, bisphosphonates have been widely used to treat a variety of bone diseases. The marked inhibitory action of bisphosphonates on osteoclast-mediated bone resorption has led to success in the treatment of pathologic processes with increased bone turnover such as Paget's disease, bone tumors, and osteoporosis. More recently, investigators have speculated on whether bisphosphonates can play an important role in fracture repair by enhancing the healing process and limiting disuse osteoporosis. Two separate studies 2,3 have evaluated the effect of bisphosphonate therapy on fracture healing in osteoporotic women with distal radius fractures. Each study assessed bone mineral density at the fracture site as the primary outcome measure. Post-fracture bisphosphonate treatment increased bone mineral den* Corresponding author. E-mail address michael.koester (M.C. Koester). The clinical relevance of increased bone mineral density within a fracture callous is...


After the diagnosis of tibial stress fracture has been made by history, physical examination, and imaging modalities, treatment needs to be initiated. The typical tibial stress fracture that occurs on the posteromedial portion of the tibia usually responds to a period of rest followed by gradual resumption of activities. It is also important to identify and modify any risk factors. Training regimen and footwear are easily correctable. Intrinsic causes such as nutritional, hormonal, or other medical abnormalities also need to be addressed. Female athletes need to be evaluated for eating disorders, amenorrhea, or oligomenor-rhea and for decreased bone density. Replacing estrogen returns the female athlete to a normal menstrual state and will likely improve bone mineral density. Clinical investigation continues into the role of medications. It has been well established that those who have nutritional deficiencies should take supplemental calcium (1500 to 2000 mg d) along with vitamin D....

Imaging Studies

Plain radiographs are not helpful for most patients early in the course of RA, as they generally show only soft tissue swelling or osteoporosis. Radiographs are indicated only to help rule out infection or fracture, when the patient has a history of malignancy, when the physical examination fails to localize the source of pain, or when pain continues despite conservative treatment. Over time, radiographs of the hands and feet in particular may show joint space narrowing, periar-ticular osteoporosis, and eventually marginal bony erosions.

Delayed Menarche

Be a marker for other possible influences on stress fracture risk, such as low body fat, low body weight, future menstrual disturbance, or excessive training. The effect of this delay on bone health and the risk of stress fractures have not been well studied however, some studies suggest osteopenia, stress fracture, and scoliosis may be potential complications of delayed menarche 53,71 . Scoliosis, in particular, has been observed in female ballet dancers with delayed menarche 71 . This may also lead to pelvic obliquity and relative leg length discrepancies and the potential for increasing the risk for stress fracture.

Hormonal Factors

Low estrogen environments in the female athlete are associated with loss of bone-mineral density, predisposing the athlete to stress fracture. Myburgh and colleagues 29 found that runners who had decreased bone-mineral density were at greater risk for stress fracture. Several studies have shown that amenor-rheic and oligomenorrheic athletes are especially at high risk of bone loss 34,37 . A complete menstrual history is required whenever a diagnosis of stress fracture is made in the young female athlete. Hormonal replacement therapy may provide some benefit in the maintenance of bone-mineral density in the amenor-rheic athlete but must be in conjunction with nutritional and lifestyle counseling.

Parathyroid Hormone

The anabolic effect that PTH has on bone is not fully understood. The effect appears to be secondary to the activation of resting osteoblasts, resulting in an increased number of circulating cells 14 . Because this action appears to depend on the existing number of cells within the bone, PTH is less active in rats with severe osteopenia 15 . PTH also stimulates osteoprogenitor cells to become osteoblasts in rats 16 , and it has been shown to postpone osteoblast apoptosis in mice 17 . Two randomized clinical trials involving women with osteoporosis have found increases in bone mass density and a decrease in fracture risk 28,29 . In 2002, the US Food and Drug Administration approved teriparatide, a synthetic form of PTH, for the treatment of osteoporosis. Although it is likely that PTH will not promote the healing of fracture nonunions because of the need for viable osteoblasts, it may play a role in the treatment of other fractures by allowing an earlier return to competition. PTH...

Future Directions

Transplantation of MSCs represents a new avenue for improved cellular therapy with potential clinical applications in hematopoietic engraftment, gene therapy, and regenerative strategies. Preliminary clinical observations of MSC cotransplants may accelerate hematopoietic reconstitution after cord-blood-derived and autologous stem cell transplantation. Transplants of MSCs expressing an intact or amplified gene for type I collagen may provide a therapeutic role in overcoming the genetic disorder in patients with osteogenesis imperfecta. Genetically modified MSCs may also provide an effective means to correct other inborn errors of metabolism. With respect to allografts, cotransplants of donor-derived MSCs may ameliorate graft-vs-host disease by their immunosuppres-sive effect (138). MSC therapy could also be an important bone engineering consideration for elderly patients (i.e., osteoporosis) (139). As for any clinical

Body Chemistry

Most of the body's chemical processes affect a variety of substances through interactions with other processes. When the level of phosphorus in the blood builds up above its normal range, for instance, it combines with calcium to form calcium phosphate. That may lower the blood level of calcium so far that too little calcium enters the skeleton, which needs it for making new bone. If this condition continues, as it may when a patient has kidney failure and can't excrete phosphorus, osteoporosis may result. Some other conditions may lead to too much calcium in the blood (hypercalcemia), a cause of kidney stones and irregular heartbeat.

Scottrade Center

Sedentary lifestyle is one of the ten leading causes of death and disability in the world 1 . Physical inactivity increases all causes mortality and the risk of cardiovascular disease, hypertension, type II diabetes, obesity, osteoporosis, colon and breast cancer, depression, and anxiety 2 . Yet, around the world, physical activity levels are decreasing, particularly among young people. It is estimated that less than 35 of young people are sufficiently active to benefit their present and future health and well-being 1 . This is discouraging for a number of reasons. First, research suggests that patterns of physical activity adopted at a young age are likely to persist into adulthood 3,4 . Second, involvement in physical activity and sports may encourage the adoption of other health behaviors such as a healthy diet, better safety practices such as seatbelt use, and the avoidance of health risk behaviors such as tobacco and alcohol use 5,6 . Thus, physical activity may influence health...

Therapeutic exercise

Limits the body's ability to increase heart rate, stroke volume and cardiac output (Ragnarsson, 1991). Evidence is mixed as to whether FES ergometry can retard or reverse the osteoporosis seen in patients with SCI. In one study of 10 spinal cord injured individuals who underwent 12 months of FES cycling 30 min per day, 3 days per week, bone mineral density of the proximal tibia increased 10 . Unfortunately, after a further 6 months of exercise but at a frequency of only one session per week, the bone mineral density reverted to pre-training levels (Mohr et al., 1997).

Stress Injury

A stress injury occurs on a continuum from normal bone remodeling and repair to frank cortical fracture. Overall bone health depends on mechanical, hor- A stress injury of bone is the result of either excessive bone strain with the accumulation of microdamage and the inability to keep up with appropriate skeletal repair (fatigue reaction or fracture) or depressed bony remodeling in response to normal strain (insufficiency reaction or fracture). The former situation most likely occurs in athletes and military recruits. The latter most likely occurs with the female athlete triad, metabolic bone disease, and osteoporosis. Sacral insufficiency stress fractures have been found to occur in female runners and often mimic the presentation of sacroiliitis. There may also be a component of reperfusion injury following prolonged strenuous exercise that results in bone tissue ischemia. This may help explain how some stress fractures occur in cortical bone areas of lower strain and when...