260 of parathyroid hormone (PTH), which stimulates the absorption of calcium through augmentation of the produc- tion of 1,25(OH)2D [2, 3]. PTH also mediates the mobilization of calcium from bone by stimulating bone resorption, which results in a reduction in bone mineral density. Chronic elevations of PTH from vitamin D deficiency are associated with increased cortical bone resorption and porosity. The relationship between vitamin D status and calcium absorption was recently studied in two small, randomized, crossover studies of postmenopausal women. Study partic- ipants received commercially available calcium supplements providing about 500 mg of calcium and 200 IU of vitamin D per day. The participants were predosed with 800 IU of 25 (OH)D on alternate days for an average of 3 weeks prior to calcium absorption measurements as a way to restore adequate vitamin D levels rapidly [4]. Compared with women who received no 25(OH)D treatment, those who did undergo this treatment demonstrated a 3.5% higher (P<0.002) serum calcium concentration prior to calcium supplement ingestion, a 16.5% lower serum PTH concentration, and a 65% greater increase in calcium absorption fraction. Vitamin D and Muscle Function During the past 10 to 20 years, many case reports have documented that in both young and old individuals, prolonged vitamin D deficiency can be associated with severe muscle weakness and disability and has been found to improve within several weeks of vitamin D supplemen- tation [5, 6]. The findings from a population-based US survey of 4100 ambulatory adults 60 years of age and older suggest an association between vitamin D status and lower extremity function [7]. Lower extremity function in study participants was assessed using an eight-foot walking-speed test, and serum 25(OH)D concentrations were determined by radioimmunoassay. Test performance speed increased as the 25(OH)D level rose throughout the reference range of the assay of 9.0 to 37.6 ng/mL, with the most significant improvement observed as 25(OH)D increased from about 10 to 17 ng/mL. Because this study used a cross-sectional design to analyze the data, a causal relationship between vitamin D concentration and lower extremity function cannot be established. The vitamin D receptor (VDR) is present in muscle cells, and the number of VDRs on each muscle cell appears to decrease with age [8]. Binding of vitamin D to its receptor results in the activation of several signaling pathways, including calcium uptake into the muscle cell, phosphate transport across the cell membrane, phospholipid metabo- lism, and muscle cell proliferation and differentiation [9 ]. Studies in chick embryo myoblasts demonstrated that short- Curr Rheumatol Rep (2010) 12:259–263 term treatment with 1,25(OH)D at roughly physiologic levels increased cell density and fusion of myocytes and had stimulatory effects on their proliferation. However, effects were not seen on the differentiation phase of myocyte development [10]. Some data also support a role for 1,25(OH)D in modulating muscle contractility [9 ]. Recent studies in VDR knockout murine models provide additional support for the direct effects of vitamin D and its receptor on skeletal muscle tissue. The VDR-null mouse (lacking the VDR) has a phenotype characterized by reduced bone size, body size, weight, motor coordination, and poor physical performance compared with wild-type mice [11]. Also, metabolic abnormalities associated with lack of the VDR include hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, bone deformity, and mus- cle fiber changes. These features were more prominent in the VDR-null mouse after weaning and with aging, suggesting a role for the VDR in skeletal development and maturation. However, VDR polymorphisms, which are subtle variations in DNA sequence of the VDR gene, exist that are associated with a range of biologic characteristics, including muscle strength. The Fok1 polymorphism involves a T/C transition in exon 2 of the VDR gene [12]. Individuals with the C allele have a shorter VDR than those with the T allele, and there is in vitro evidence for enhanced activity of VDR as a transcription factor. Clinically, the C allele has been associated with reduced fat mass and quadriceps strength [12]. More work may be warranted to link signaling through the VDR in muscle with its potential functional consequences. Muscle biopsies from adults with profound vitamin D deficiency had shown predominant type II fiber atrophy. As type II muscle fibers are the initial fibers to be recruited for balance and coordination, this may explain some of the tendency for increased falls in individuals who are vitamin D deficient. Histologic sections of type II muscle fibers show enlarged interfibrillar spaces and infiltration of fat, fibrosis, and glycogen granules [13, 14]. Two small studies have evaluated vitamin D supplemen- tation and muscle fiber composition. One randomized controlled clinical trial of older adult stroke victims found that 1000 IU of vitamin D2 over a 2-year period increased percentage and mean diameter of type II muscle fibers [14]. Furthermore, serum 25(OH)D level was correlated with both the baseline type II muscle fiber diameter and the diameter after 2 years of follow-up. A few clinical trials have evaluated the combination of calcium and vitamin D to determine whether this kind of supplement might alter the risk of falling in older adults. A double-blind, randomized trial in Switzerland studied the effect of vitamin D and calcium supplementation on the risk of falling among 122 women (mean age, 85.3 years) cared for in long-term geriatric care units before transfer into nursing