Curr Rheumatol Rep (2010) 12:259–263 homes. Study participants were randomly assigned to receive 1200 mg/d of calcium alone or calcium 1200 mg/d plus 800 IU/d of vitamin D for 12 weeks. The mean serum 25(OH) D concentration prior to treatment was 12 ng/mL in both treatment groups. Vitamin D and calcium supplementation accounted for a 49% reduction in the risk of a fall (P=0.01) after adjusting for 1) age, 2) the number of participants who fell during a 6-week pretreatment period, 3) the number of falls per person during the pretreatment period, 4) baseline serum levels of 25(OH)D and 1,25(OH)2D, and 5) the observation time during treatment. This reduction may be attributable to the significant improvement (P=0.0094) in musculoskeletal function detected in patients who received vitamin D and calcium. Because of a high number of transfers to nursing homes, the dropout rate in this study was high. All study participants were institutionalized older European women from Switzerland, so the study results may not be generalizable across a more broad population [15]. Bischoff et al. [15] performed a meta-analysis of several small clinical studies that evaluated the effect of vitamin D treatment compared with control groups on the risk of falling and found that vitamin D replacement favored a reduction in number of falls, with an overall OR of about 0.75. Vitamin D and Bone Mass and Fractures The most important determinants of the risk of skeletal fracture are low bone mass, microarchitectural deterioration, and a propensity to fall. Adequate vitamin D is critical for bone formation. Higher levels of 25(OH)D have been associated with higher bone mineral density at the hip in young and older men and women from the Third National Health and Nutrition Examination Survey at levels up to 36.8 ng/mL [16], and supplementation of vitamin D in older adults also prevents bone loss [17]. A recent study from the Women’s Health Initiative cohort also confirmed that women who had a hip fracture had significantly lower 25(OH)D values than controls. Also, women in the lowest quartile for 25(OH)D had a nearly 1.7-fold higher risk of hip fracture than women in the higher quartile for 25(OH)D [18 ]. Nutritional vitamin D deficiency causes insufficient mineralization of bone tissue and rickets in growing children and osteomalacia in adults. The active form of vitamin D, 1,25(OH)D, stimulates the absorption of calcium and phosphorus from the gastrointestinal tract, thereby making calcium and phosphorus available for mineralization. In mild vitamin D deficiency, the elevation of serum PTH increases the conversion of 25(OH)D to 1,25(OH)D to compensate for the insufficient 25(OH)D available; however, elevation in PTH increases bone resorption, leading to additional bone loss [19]. Clinical osteomalacia usually is present with severe vitamin D deficiency at levels of 5 ng/mL or less. The 261 clinical manifestations of osteomalacia include bone pain, muscular weakness generally of the proximal shoulder and hip girdle, and difficulty walking. If the calcium is also low in patients with osteomalacia, symptoms of low calcium, such as tetany or seizures, may be present. Fractures of the bone may occur because the quality of the bone in osteomalacia with reduced mineralization is more fragile than bone of normal mineral quality. A transiliac bone biopsy after fluorochrome labeling is required to confirm the diagnosis of osteomalacia. The specimens should be stained with Goldner or von Kossa stains for mineralizing surface. The bone histology section has less than 5% nonmineralized bone matrix or osteoid. However, with osteomalacia, the osteoid surface may be as high as 70%, and bone resorption may be slightly increased due to secondary hyperparathy- roidism [19]. Vitamin D as a Treatment to Prevent Osteoporotic Fractures A randomized, double-blind trial in the United Kingdom examined the effect of oral vitamin D supplementation on the risk of fracture in 2686 men and women 65 to 85 years of age who were living in the community. Study partic- ipants were randomly assigned to receive a single oral dose of 100,000 IU of vitamin D3 or matching placebo every 4 months for 5 years, which is equivalent to a daily dose of about 800 IU. The incidence of fracture of the hip, wrist, forearm, or vertebrae was 4.5% in volunteers assigned to receive vitamin D and 6.5% in those given placebo (P= 0.02), and the age-adjusted relative risk of fracture at these sites was 33% lower with vitamin D. To maximize generalizability, exclusion criteria were minimal. However, this approach introduces increased variables that can hamper the interpretability of the findings. The data were ascertained via self-report questionnaire, which could have led to ascertainment errors [20]. In another study, institu- tionalized older adult women in France were randomly assigned to calcium and vitamin D, 800 IU/d, or placebo for 18 months. Hip and other nonvertebral fracture rates were reduced by nearly 40% in the treated participants compared with the placebo group [21]. Vitamin D Intake Requirements In 1997, the Institute of Medicine of the National Academy of Sciences made recommendations for vitamin D intake. The recommendations are as follows: & Adults up to 50 years of age: supplementation with 5 µg/d, or 200 IU