Should perimenopausal women be screened for osteoporosis?

The increasing availability of noninvasive methods for measuring bone mass raises the issue of whether perimenopausal women should routinely have such measurements to identify those at risk for osteoporotic fractures of the hip, wrist, and spine. Although the mortality and morbidity caused by hip fractures would warrant routine screening, measurement of bone mass has uncertain value in assessing the risk for hip fracture. Wrist fractures generally cause only transient disability, and measurement of bone mass may not reliably predict risk. Measurements of bone density of the spine might be better able to assess a woman's risk for vertebral fractures, but the value of screening depends on whether the findings would affect a woman's decision about using estrogen therapy after menopause. Serial measurements of bone mass to estimate a woman's rate of bone loss are relatively imprecise, increase the cost of screening, and have at best a limited role in screening women to assess risk for osteoporotic fractures.     

Osteoporosis in men

Osteoporosis is characterized by a reduction in bone density, associated with skeletal fragility and an increased risk of fracture after minimal trauma. Although osteoporosis is generally considered to be a condition affecting post-menopausal women, it is now clear that substantial bone loss occurs with advancing age in men, such that up to 20% of symptomatic vertebral fractures and 30% of hip fractures occur in men. This chapter highlights the incidence and prevalence of osteoporotic fractures in men and reviews the associated morbidity, excess mortality and health and social service expenditure. The determinants of peak bone mass and bone loss in men are discussed, as is the pathogenesis of osteoporosis and vertebral and hip fractures. The criteria for the diagnosis of osteoporosis in men are reviewed, together with the most appropriate investigations for secondary osteoporosis. The management of osteoporosis in men is also discussed, highlighting the most appropriate treatment options.     

Pattern of bone mineral density in idiopathic male osteoporosis

The mechanisms of male idiopathic osteoporosis are little known. We evaluated bone mineral loss by dual-energy X-ray absorptiometry and determined its cortical or trabecular nature in a cohort of men with idiopathic osteoporosis with fractures. Thirty-nine men (mean age 60?±?13?years), with negative investigations for the cause of osteoporosis, were studied. All had fragility fractures: vertebral 51%, peripheral 25%, and both types 24%. Bone density was measured at the lumbar spine (L2-L4), total hip and whole body. The limb/axial skeleton (spine?+?hips) and hip/L2-L4 BMD ratios were calculated. Serum 25-hydroxy-vitamin D, PTH, bone alkaline phosphatase and CTX were measured. Bone mineral loss predominated at the lumbar spine (mean L2-L4 T-score -3?±?0.93, mean total hip T-score -1.87?±?0.75). Limb/axial skeleton and total hip/L2-L4 BMD were strongly correlated, but not hip and spine BMD. The ratio values were widely scattered, indicating markedly heterogeneous bone loss. Vitamin D, PTH, bone alkaline phosphatase and CTX levels did not differ between predominantly trabecular and cortical osteoporosis. Bone mineral density measurement in male idiopathic osteoporosis with fractures demonstrated that bone loss predominated in the spine and that it was very heterogeneous, principally affecting cortical or trabecular bone depending on the patient.     

Glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis is the most frequent cause of secondary osteoporosis. Glucocorticoids cause a rapid bone loss in the first few months of use, but the most important effect of the drug is suppression of bone formation. The administration of oral glucocorticoid is associated with an increased risk of fractures at the spine and hip. The risk is related to the dose, but even small doses can increase the risk. Patients on glucocorticoid therapy lose more trabecular than cortical bone and the fractures are more frequent at the spine than at the hip. Calcium, vitamin D and activated forms of vitamin D can prevent bone loss and antiresorptive agents are effective for prevention and treatment of bone loss and to decrease fracture risk. Despite the known effects of glucocorticoids on bone, only a few patients are advised to take preventive measures and treat glucocorticoid-induced osteoporosis.     

Pharmacological treatment of osteoporosis for people over 70

Osteoporosis has been defined as "a systemic disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture". The impact of osteoporosis is most pronounced in elderly populations who run the greatest risk of fractures. The probability of developing mainly hip, vertebral and other non-vertebral fractures (for example, a Colles fracture) not only depends on bone mineral density (BMD) but also on age. Older patients are more susceptible to fracture than younger patients with the same BMD T-score. As the older population increases, the incidence of osteoporotic fractures is expected to rise dramatically over the next few decades. Although hip fractures are considered to be the most severe and economically important osteoporotic fracture, vertebral fractures also lead to adverse health outcomes, including back pain, height loss and kyphosis. These changes may result in significant declines in physical performance, function and, ultimately, loss of independence. The challenge for physicians is to prevent bone loss, to diagnose and treat osteoporosis before fractures occur, and to treat patients who have already experienced a fracture to prevent recurrent fractures. The objective of this review is to analyze the capacity to reduce fractures as the key element to evaluate the effectiveness of available medications: calcium and Vitamin D, bone formation drugs, antiresortive drugs, and dual-effect drugs. In view of the paucity of information about treatment of osteoporosis in the elderly population, available studies were not designed with this objective, so that this article reviews data mostly deriving from post-hoc analysis or sub-analysis of the main phase III clinical trials of each of the tested medications.     

Osteoporosis and fractures in postmenopausal women using estrogen

BACKGROUND: Previous studies demonstrate that postmenopausal women who use estrogen are somewhat protected from bone loss and fractures compared with nonusers, but the extent to which estrogen users remain at risk for osteoporosis and fractures is uncertain. OBJECTIVE: To determine long-term probabilities for incident fractures among postmenopausal estrogen users. METHODS: We examined data from the Study of Osteoporotic Fractures, a prospective cohort study with 10 years of follow-up (1986-1999). This cohort includes 8816 women 65 years and older from community settings in 4 areas of the United States. MAIN OUTCOME MEASURES: Hip, wrist, vertebral, and nonvertebral fractures. RESULTS: At baseline, using criteria developed by the World Health Organization, 40% of continuous estrogen users were osteopenic and 13% were osteoporotic at the hip or spine. Although women currently using estrogen lost less bone density than past users or those who never used estrogen, all user groups on average lost bone from the hip and calcaneus. During 10 years of observation, the adjusted probability of nonvertebral fractures was 19.6% for continuous estrogen users, similar to current partial users and lower than past users and those who never used estrogen (P<.05). These comparisons were similar for hip, wrist, and vertebral fractures. CONCLUSIONS: Although estrogen use is associated with reduced prevalence of low bone density, less bone loss, and lower probabilities for fractures, osteoporosis and fractures are common in older women who used estrogen continuously since menopause. Estrogen users should be considered in strategies designed to detect, prevent, and treat osteoporosis.     

Aortic calcification and the risk of osteoporosis and fractures

We investigated the relation between computed tomography measures of aortic calcification and values for bone density and the number of fragility fractures in 2348 healthy, postmenopausal women. To determine whether increases in vascular calcification and bone loss progress in parallel, baseline values were compared with measurements obtained 9 months to 8 yr later in a subgroup of 228 women. Of the 2348 subjects studied, 70% had osteoporosis, 30% had at least one vertebral fracture, and 9% had at least one hip fracture. Aortic calcifications were inversely related to bone density and directly related to fractures. After adjusting for age and potential confounders, measures for aortic calcification predicted 26.1% of the variance in bone density (P < 0.001). Compared with women without calcification, the odds ratios for vertebral and hip fractures in those with calcification were estimated to be 4.8 (95% confidence interval, 3.6-6.5) and 2.9 (95% confidence interval, 1.8-4.8), respectively. The subgroup analysis of 228 women longitudinally studied showed that the percentage of yearly increase in aortic calcification accounted for 47% of the variance in the percentage rate of bone loss (P < 0.001). Moreover, a strong graded association was observed between the progression of vascular calcification and bone loss for each quartile. Women in the highest quartile for gains in aortic calcification had four times greater yearly bone loss (5.3 vs.1.3% yearly; P < 0.001) than women of similar age in the lowest quartile. Smaller, but highly significant differences were also found between all other quartiles. We conclude that aortic calcifications are a strong predictor for low bone density and fragility fractures.     

Discriminating Factors Between Hip and Other Fractures in Older Women

Objective: To elucidate discriminating factors between femoral neck and other fractures in older women. Method: A case-control study of 110 women aged 60 to 91 years. Results: Both cases and controls had reduced bone density, with no significant difference evident between the groups. Hip fracture subjects were older, had lower BMI scores and were more likely to have fallen sideways or backward. The controls were more likely to be taking prednisone. Conclusions: The prevention of hip fractures may depend on strategies such as excessive weight loss prevention, enhancement of strength and provision of local hip protection, in addition to strategies aimed at maintaining bone density.     

Hypovitaminosis D and 'functional hypoparathyroidism'-the NoNoF (Nottingham Neck of Femur) study.

BACKGROUND: calcium and vitamin D deficiency are common in elderly people and lead to increased bone loss, with an enhanced risk of osteoporotic fractures. Although hip fractures are a serious consequence, few therapeutic measures are given for primary or secondary prevention. A combination of calcium and vitamin D may not be the most effective treatment for all patients. OBJECTIVE: to investigate the effects of hypovitaminosis D on the calcium-parathyroid hormone endocrine axis, bone mineral density and fracture type, and the optimal role of combination calcium and vitamin D therapy after hip fracture in elderly patients. DESIGN: a population-based, prospective cohort study. METHODS: 150 elderly subjects were recruited from the fast-track orthogeriatric rehabilitation ward within 7 days of surgery for hip fracture. This ward accepts people who live at home and are independent in activities of daily living. All subjects had a baseline medical examination, biochemical tests (parathyroid hormone, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) and were referred for bone densitometry. RESULTS: at 68%, the prevalence of hypovitaminosis D (25-hydroxyvitamin D<30 nmol/l) was high. However, only half the patients had evidence of secondary hyperparathyroidism, the rest having a low to normal level of parathyroid hormone ('functional hypoparathyroidism'). Patients with secondary hyperparathyroidism and hypovitaminosis D had a higher mean corrected calcium, higher 1,25-dihydroxyvitamin D, lower hip bone mineral density and an excess of extracapsular over intracapsular fractures than the 'functional hypoparathyroid' group (P<0.01). CONCLUSION: there is a high prevalence of hypovitaminosis D in active, elderly people living at home who present with a hip fracture. However, secondary hyperparathyroidism occurs in only half of these patients. This subgroup attempts to maintain calcium homeostasis but does so at the expense of increased bone turnover, leading to amplified hip bone loss and an excess of extracapsular over intracapsular fractures. Combination calcium and vitamin D treatment may be effective in preventing a second hip fracture in these patients, but its role in patients with hypovitaminosis D without secondary hyperparathyroidism and 'vitamin D-replete' subjects needs further evaluation.     

Hip fracture protection by alendronate treatment in postmenopausal women with osteoporosis: a review of the literature

Osteoporosis most commonly affects postmenopausal women, placing them at a significant risk of fractures. In particular, hip fractures are an important cause of mortality and morbidity among postmenopausal women. Anti-resorptive therapies that produce greater decreases in bone turnover markers together with greater increases in bone mineral density (BMD) are associated with greater reductions in fracture risk, especially at sites primarily composed of cortical bone such as the hip. Thus, treatment with potent anti-resorptive drugs like alendronate is a strategy for preventing hip fractures in postmenopausal women with osteoporosis. The purpose of this paper is to discuss the efficacy of alendronate against hip fractures and the mechanism for this anti-fracture efficacy in postmenopausal women with osteoporosis. A meta-analysis of randomized controlled trials has shown that alendronate reduces the risk of hip fractures by 55% in postmenopausal women with osteoporosis. According to the analyses of the Fracture Intervention Trial, each 1 standard deviation reduction in a 1-year change in bone-specific alkaline phosphatase (BSAP) is associated with 39% fewer hip fractures in alendronate-treated postmenopausal women, and those with at least 30% reduction in BSAP have a 74% lower risk of hip fractures relative to those with less than 30%. Alendronate is effective in reducing the risk of hip fractures across a spectrum of ages. The mechanism for this anti-fracture efficacy has been clarified; alendronate strongly suppresses bone turnover and subsequently increases hip BMD, decreases cortical porosity, improves parameters of hip structure geometry (cortical thickness, cross-sectional area, section modulus, and buckling ratio), and produces more uniform mineralization (increases the mean degree of mineralization of bone) in cortical bone. A once-weekly regimen of alendronate administration provides better patient compliance and persistence with the treatment than the once-daily dosing regimen, leading to greater efficacy against hip fractures. Thus, the efficacy of alendronate against hip fractures has been confirmed in postmenopausal women with osteoporosis, especially with a once-weekly dosing regimen.     

Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip

OBJECTIVE: To investigate whether aorta calcification (AC) - a surrogate marker of atherosclerosis - is an independent indicator of low bone mass density (BMD), accelerated bone loss, and risk of future fractures in postmenopausal women. DESIGN: A prospective epidemiological study. Follow-up period was 7.5 years. SETTING: Community-based sample followed by a research institute. SUBJECTS: A total of 2662 generally healthy postmenopausal women with a mean age of 65.0 +/- 7.1 years at baseline. MAIN OUTCOME MEASURES: Annual rate of changes in BMD (DEXA) and AC (X-rays), vertebral fractures (X-rays), hip fractures (questionnaire). RESULTS: Advanced AC at baseline was significantly associated with lower BMD and accelerated bone loss from the proximal femur. In a multivariate logistic regression model, age (OR 1.1, 95% CI 1.0-1.2, P = 0.02), body mass index (BMI; OR 0.9, 95% CI 0.8-1.0, P = 0.03) and the severity of AC (OR 2.3, 95% CI 1.1-4.8, P = 0.03) were independent predictors of hip fractures. Adjusted OR for vertebral fracture was 1.2 (95% CI 1.0-1.5, P = 0.12). CONCLUSIONS: Aorta calcification seems to independently contribute to the development of osteoporosis in the proximal femur. Further studies are needed to clarify whether effective atherosclerosis prevention lowers hip fracture risk.     

Evaluation and treatment of bone disease after fragility fracture

Bone mineral density and other measuring tests are part of the risk assessment of primary and secondary osteoporosis necessary in treating patients after fragility fracture. A better understanding of factors contributing to insufficiency fracture in osteoporotic bone is essential to guide the clinician's intervention in this disease affecting 25 million women in the United States and responsible for an estimated 700,000 vertebral and 300,000 hip fractures every year. Prevention of future fractures by slowing or stopping bone loss, maintaining bone strength, and minimizing or eliminating factors contributing to fractures, through pharmacotherapy, education, and lifestyle changes, can help slow annual health care expenditures for osteoporotic fractures, which now exceed 17 billion dollars, more than for breast and gynecological cancers combined.     

Approach to the prostate cancer patient with bone disease

Prostate cancer is the most common visceral malignancy in men. Androgen deprivation therapy (ADT) is commonly used in patients with nonmetastatic prostate cancer and is associated with significant bone loss and fractures. The greatest bone loss occurs during initiation of ADT. Men should have assessment of skeletal integrity with bone mineral density examination by dual x-ray absorptiometry of the hip and spine. Men with fragility fractures or osteoporosis by bone density should be considered for bisphosphonate therapy. Men with low bone mass may need antiresorptive therapy, depending on other risk factors. Men with a normal bone mineral density should be followed up closely with bone densitometry while on ADT. All men should receive preventive measures with calcium (1200 mg daily in divided doses), vitamin D (800-1000 IU/d), and weight-bearing exercise. Men should be evaluated for additional secondary causes of bone loss including vitamin D insufficiency. Guidelines are needed for androgen-induced bone loss screening and treatment.     

THE DIAGNOSTIC VALIDITY OF LOCAL AND TOTAL BONE MINERAL MEASUREMENTS IN POSTMENOPAUSAL OSTEOPOROSIS AND OSTEOARTHRITIS

Assessment of different forms of prevention and treatment of bone mineral loss depends upon valid and precise methods to assess bone mass. We have here studied four groups of women: 45 healthy premenopausal women, 37 healthy postmenopausal women, 21 women with osteoarthritis and 20 with hip fractures. Bone mass was measured in the spine and total body by dual photon absorptiometry and in two forearm sites (proximal and distal bone mineral content (BMC) by single photon absorptiometry. The long-term (1 year) reproducibility was 1.2% for proximal BMC, 1.6% for distal BMC, 5.5% for spinal BMC, and 2.1% for total body bone mass (TBBM). In the early postmenopausal years bone mass was mainly reduced in areas with a high content of trabecular bone. In elderly postmenopausal women and women with hip fractures bone mass was almost identical in all four sites studied. The osteoarthritic patients had an 18% reduction of bone mass in the forearms and in TBBM, whereas the spinal bone mass was only reduced by 6%. In all subgroups TBBM could be predicted from the forearm measurements with standard errors of estimates of 9-13%. When the osteoarthritic women were excluded spinal bone mass could be predicted from both forearm measurements with a standard error of 15% (r = 0.74). The distal forearm BMC seems to be a more accurate estimate of spinal bone mass than does the proximal measurement. Of the 20 patients with hip fracture 16 had a distal forearm value below the premenopausal normal range, whereas spinal bone mass was subnormal in only eight (P less than 0.05). We conclude that bone loss is universal in patients with hip fracture and measurements of forearm bone mass will meet most clinical and research demands.     

Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60

Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.     

Volumetric bone density at the femoral neck as a common measure of hip fracture risk for men and women

Measurements of bone density using dual-energy x-ray absorptiometry are generally based on the areal projection, which incompletely accounts for size. The larger areal bone density in older men compared with older women is primarily due to their larger bone size, conferring a biomechanical advantage that may be a major factor contributing to lower hip fracture rates. The aim of this study was to evaluate estimated volumetric bone density at the hip in men and women with and without fractures to better determine the role of estimated volumetric density vs. size in hip fracture risk. This prospective population-based study compared 852 women and 635 men without fractures with 73 women and 23 men with hip fractures. As expected, areal bone mineral density (BMD) and cross-sectional area were lower in women than men, and areal bone density was lower in those with hip fractures compared with nonfracture subjects. However, estimated volumetric BMD was the only parameter, apart from age, that was the same in women and men both without hip fractures (0.31 +/- 0.06 and 0.31 +/- 0.06 g/cm3, respectively) and with hip fractures (0.25 +/- 0.04 and 0.26 +/- 0.04 g/cm3, respectively). Using the World Health Organization 2.5 SD cut-off for osteoporosis for hip fracture prediction, estimated volumetric BMD was more sensitive than areal BMD in men (70 vs. 43%; P = 0.04) and similar to that in women, in whom sensitivity was similar for both areal (73%) and estimated volumetric (78%) BMD cut-offs. Thus, men and women have hip fractures at the same estimated femoral neck volumetric BMD, which is largely independent of the size artifact inherent in areal BMD. This aspect of estimated femoral neck volumetric BMD suggests that it can provide a single measure that could be used in men and women. It needs further exploration for a role in assessment of hip fracture risk across the sexes and particularly in men.     

Selection of individuals for prevention of fractures due to bone fragility.

Most patients with fractures go untreated because of the lack of awareness of osteoporosis. Treatment is indicated for women and men with osteoporosis and women and men with fractures with either osteoporosis or osteopenia because (a) fractures increase morbidity and mortality, (b) the burden of fractures is increasing because longevity is increasing, and (c) bone loss accelerates, rather than decelerates in old age. The indication for drug therapy is less clear in women or men with osteopenia because drugs have not been proved to reduce fracture risk in this group. There is no evidence that treating individuals with only risk factors reduces the fracture rate. Screening has not been shown to reduce the burden of fractures. Altering the bone mineral density by a few percent in the population is likely to reduce the number of fractures, but how this can be achieved is unknown. The rigorously investigated drugs reducing the spine fracture rate are alendronate, raloxifene and risedronate. Calcium and vitamin D reduce hip fractures in nursing home residents but not community-dwellers. In the community, only alendronate and risedronate have been reported to reduce hip fractures in randomized trials. The evidence for hormone replacement therapy is less satisfactory. It is likely to reduce the number of spinal fractures, but its role in hip fracture prevention is uncertain. Only alendronate has been reported to reduce spine fractures in men with osteoporosis. Evidence for the use of other drugs (calcitonin, fluoride, anabolic steroids and active vitamin D metabolites) in women or men is insufficient to justify their use.     

Pathogenesis of osteoporosis.

Osteoporosis is a very common disorder affecting millions of post-menopausal women and men of various ages. Although the disease is manifested by painful fractures of the spine, hip or radius, the underlying pathogenesis is complex and multifactorial. One of the strongest predictors of future osteoporotic fractures is low bone mineral density. The determinants of adult bone density include the rate of bone acquisition during adolescence and the absolute loss of bone during the six decades of adult life. Recent studies have clarified how bone mass is acquired during the early teen years in both boys and girls. Genetic factors play an enormous role in defining the height of acquisition of bone mass; however, these factors also interact with environmental and hormonal determinants. Many more studies have focused on adult bone loss. Disorders in bone remodelling result in an imbalance in bone turnover, favouring resorption over formation. Systemic factors such as oestrogen deprivation and parathyroid hormone strongly activate remodelling and can, in several circumstances, lead to imbalances in the remodelling cycle. The molecular cues that couple bone formation to resorption have recently been elucidated, and those factors may themselves become therapeutic targets for future treatment regimens to prevent osteoporosis and its resultant fractures.     

Heterogeneity of fracture syndromes in postmenopausal women

Studies were performed on 32 women with vertebral crush fractures (mean age, 65.1 yr) and 27 patients with recent hip fractures (mean age, 83.6 yr). Histomorphometric analysis of undecalcified transiliac crest biopsies revealed significant differences between the two fracture groups. Trabecular bone volume (TBV) was significantly lower in vertebral fracture than in hip fracture patients (12.0 +/- 4.4% (+/- SD) vs. 14.8 +/- 3.6%; P = 0.014), while thickness of cortices was significantly lower for hip fracture than for vertebral fracture patients (436 +/- 231 vs. 823 +/- 465 microns; P less than 0.001). The TBV and radial bone mass (measured by absorptiometry on the shaft) for the vertebral fracture group were significantly lower than age-expected values. For the patients with hip fractures, the TBV was significantly above the expected value, and radial bone mass was not significantly different from the expected value. Other quantitative histological measurements did not generally differ between the two fracture groups and were compatible with normal or increased bone remodeling. The serum PTH in the hip fracture group was significantly increased above that expected in normal women of similar age. These data demonstrate the anatomical heterogeneity of osteoporotic fracture syndromes. Patients with vertebral fractures have an early deficit of trabecular bone for their age, while those with hip fractures have a deficit of both cortical and trabecular bone compared to women of age 50 yr, but the deficit is not excessive compared to others of similar age without fractures.     

Epidemiology of osteoporosis

Osteoporosis and related fractures represent a major, and growing, public health concern for the United States and worldwide. The pathogenesis of osteoporosis is complex, requiring attention to the different life phases involved in growth, maintenance, and loss of bone, in addition to non-skeletal factors associated with falls and fractures. While the current clinical definition is based upon bone density measurements, other determinants of skeletal strength, particularly bone quality, are important to identify for future areas of research and prevention efforts. This epidemiologic review describes the definition, pathogenesis, and risk factors, as well as the frequency and impact of osteoporosis, with particular emphasis upon hip fracture.