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This study of pooled data from trials of oral vitamin D supplementation examined the incidence of hip and nonvertebral fractures in persons 65 years of age or older. The data suggest that high-dose vitamin D may help prevent hip and nonvertebral fractures. Approximately 75% of fractures occur in people 65 years of age or older. 1 By 2050, the worldwide incidence of hip fractures is expected to increase by 240% among women and 310% among men. 2 One strategy to prevent fractures in this population might be universal vitamin D supplementation. However, the results of several study level meta-analyses and one pooled participant-level analysis do not agree. Although one trial-level meta-analysis of double-blind, randomized, controlled trials suggested an 18% reduction in the incidence of hip fracture and a 20% reduction in the incidence of any nonvertebral fracture at a received dose of no less . . .

Hip fractures cause substantial disability and are associated with a high rate of death among elderly women, 1 but there have been few studies of the effects of drug treatment on the risk of hip fracture. Observational studies suggest that estrogen may reduce the risk of hip fracture. 2 – 4 Alendronate reduced the risk of hip fracture in postmenopausal women with low bone mass at the femoral neck or with previous vertebral fractures, but not in women without those risk factors. 5 , 6 Numerous risk factors for hip fracture have been identified. 7 – 13 In general, these risk factors can be categorized as skeletal . . .

Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Deleterious effect of oral corticosteroids on bone has been well documented, whereas this remains debated for inhaled ones (ICS). Our objectives were to analyze the effects of ICS on bone mineral density, fracture risk and bone markers. We performed an exhaustive systematic research of all controlled trials potentially containing pertinent data, peer-reviewed by a dedicated WHO expert group, and comprehensive meta-analyses of the data. Inclusion criteria were ICS, and BMD/markers/fractures in asthma/chronic obstructive pulmonary diseases (COPD) and healthy patients. Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, study design and ICS type. Results were expressed as standardized mean difference/effect size (ES), relative risk (RR) or odds ratio (OR), depending on study design and outcome units. Publication bias was investigated. Twenty-three trials were reviewed; 11 papers fit the inclusion criteria and were assessed for the main analysis. Quality scores for the randomized controlled trials (RCTs) were 80%, 71% for the prospective cohort studies, and 78% for the retrospective cohort and cross-sectional studies. We globally assessed ICS effects on BMD and found deleterious effects: ES=0.61 ( p=0.001) for healthy subjects, and ES=0.27 ( p<0.001) for asthma/COPD patients. For these patients, this effect was 0.21 ( p<0.01) at the lumbar spine, and 0.26 ( p<0.001) at the hip or femoral neck. A single study evaluated the impact of ICS on hip fracture and reported an increased OR of 1.6 (1.24; 2.03). Lumbar fracture rate differences did not reach the level of statistical significance: 1.87 (0.5; 6.94). Osteocalcin and PICP were decreased and ICTP, pyridinoline and deoxypyridinoline levels were not significantly affected. Budesonide (BUD) appeared to be the ICS inducing the less deleterious effects on bone, followed by beclomethasone dipropionate (BDP) and triamcinolone (TRI). Publication bias investigation provided non-significant results. In our meta-analyses, BUD at a mean daily dose (SD) of 686 microg (158 microg), BDP at 703 microg (123 microg) and TRI at 1,000 microg (282 microg) were found to affect bone mineral density and markers in patients suffering from the two major respiratory diseases. These findings could have practical implication in the long-term management of asthmatic and COPD patients.

Bisphosphonates ameliorate osteoporosis, yet gastrointestinal side effects have limited patients' adherence to oral regimens. Intermittent intravenous therapy is effective, but the optimal interval between doses is unknown. This study examined five intravenous regimens of the potent bisphosphonate zoledronic acid (a total of 1 to 4 mg in one to four doses over the course of one year) and compared them with placebo in postmenopausal women with low bone mineral density. In postmenopausal women with low bone mineral density, an annual infusion of this potent bisphosphonate may be effective therapy. Oral bisphosphonates are widely used for treating osteoporosis and have been shown to increase bone mineral density and decrease the rate of fracture. 1 , 2 However, they do have limitations related to long-term compliance, gastrointestinal intolerance, and poor and variable absorption from the gastrointestinal tract. Intermittent intravenous administration of bisphosphonates might address some of these problems and has been shown to be effective in the treatment of malignant hypercalcemia and Paget's disease and to reduce the rate of skeletal complications in patients with breast carcinoma or multiple myeloma. Evidence suggests that intravenous bisphosphonates increase bone mineral density in patients with osteoporosis, . . .

Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known. Methods. We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women. Results. Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P 0.001). Conclusions. Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women

Paget's disease of bone is a localized, monostotic or polyostotic disease characterized by increased bone remodeling, bone hypertrophy, and abnormal bone structure that leads in symptomatic patients to pain and bone deformity. Complications involve the bones (fractures and neoplastic degeneration), joints (osteoarthritis), and nervous system. The short-term objective of treatment is to alleviate bone pain, and the long-term objective is to minimize or prevent the progression of the disease. Pathology, Epidemiology, and Etiology Pagetic bone is characterized by major disorganization in both the architecture and the lamellar texture of bone. These abnormalities are the results of major disturbances in bone . . .

Many postmenopausal women have a calcium intake far below the recommended amount and, in addition to attempting to improve their diet, need a calcium supplement. The aim of the study was to assess the effects of the consumption of a high calcium mineral water (HCaMW) on biochemical indices of bone remodeling in postmenopausal women with low Ca intake. A 6-month randomized double-blind placebo-controlled trial was designed to assess the effects of a daily consumption of 1 liter of a HCaMW (596 mg Ca/l) on serum parathyroid hormone (PTH) and biochemical markers of bone remodeling in postmenopausal women with a dietary Ca intake lower than 700 mg/day. The placebo group drank 1 liter of a mineral water with a low calcium content (10 mg/l). One hundred eighty healthy women were recruited (mean age: 70.1+/-4.0 years); 152 completed the 6-month trial. The changes from baseline of biochemical indices after 6 months consisted of a significant 14.1% decrease of serum PTH, osteocalcin (-8.6%), bone alkaline phosphatase (-11.5%), serum (-16.3%) and urine (-13.0%) type-1 collagen C-telopeptide in the HCaMW group compared to the placebo group, where all biochemical indices increased after 6 months. The additive effect of a small vitamin D supplement (400 iu/day) was also evaluated. In women receiving vitamin D in addition to HCaMW, the decrease in bone indices was not found to be greater than in women drinking only the HCaMW. A daily supplement of 596 mg of Ca through the consumption of 1 l of HCaMW was able to lower serum PTH and the indices of bone turnover in postmenopausal women with a low Ca intake. This could contribute to the repair of calcium deficiency and to the reduction of age-related bone loss in this population.

Summary points Paget's disease is a localised monostotic or polyostotic progressive bone disease of uncertain origin (it may be caused by a slow viral infection) It is characterised by increased bone remodelling, leading to pain, fractures, and deformities with the risk of skeletal, articular, or neurological complications Radiography, scintigraphy, and bone biochemistry are useful tools in achieving a positive diagnosis The primary aim of treatment is to reduce pain and the risk of developing long term complications Potent antiresorptive drugs are now available which control the increased bone remodelling and have led to a dramatic improvement in treatment