Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women

Abstract

anzctr.org.au Identifier: ACTRN12605000658617; isrctn.org Identifier: ISRCTN83409867.

Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens

“…Moreover, for the first time, the effects of three different calcidiol regimens on core parameters of bone and mineral homeostasis in postmenopausal women with vitamin D inadequacy (i.e., serum 25(OH)D levels less than 30 ng/ml) have been assessed. The results confirm calcidiol's prompt efficacy in correcting vitamin D status and underline its safety, at least in the short/medium term, also in regard to some non-classical, unwanted adverse events (e.g., alterations in bone turnover markers or increased fall rate) observed during supplementation with native vitamin D [11,21,22,25].…”

“…This can be exploited particularly when vitamin D status has to be optimized in a short interval of time, for example when antifracture therapy has to be undertaken in subjects at high risk for fracture (e.g., after a major fragility fracture or when commencing glucocorticoid therapy). The rapidity in correcting profound vitamin D deficiency with overt or insidious osteomalacia makes calcidiol a good alternative to the mega doses of parental vitamin D 3 , recently linked to increased falls and fractures [21,22], since the non- [14,35].…”

“…Although the high doses of cholecalciferol (up to 10,000 IU per day) are safe as far as the classic side effects (hypercalciuria and hypercalcemia) are concerned [19,20], unphysiologically high annual doses of vitamin D (300,000 to 500,000 IU) have been associated with an increased risk in falls and fractures [21,22]. Notably, beyond the major endpoints such as falls and fractures, recent studies also suggested that bolus doses of 100,000 IU vitamin D 3 and above might increase bone resorption markers significantly and dose-dependently [23,24].…”

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

“…However, cross‐sectional studies do not agree on the 25(OH)D threshold level needed to maximize BMD and even suggest that BMD may not improve with vitamin D supplementation once baseline levels of 25(OH)D are >20 ng/mL 153. Moreover, chronic 25(OH)D levels >40 ng/mL (100 nmol/L) after a single annual dose of 500 000 IU of cholecalciferol increased the risk of fractures 167. Interventional data are lacking in CKD patients, and the optimal 25(OH)D concentration for fracture risk reduction may only be inferred from observational studies 133.…”

“…Although the safety margin to minimize the risk of hypercalcaemia as 25(OH)D equal to 100 ng/mL (250 nmol/L), there are some concerns at serum 25(OH)D levels above 50 ng/mL (125 nmol/L). These concerns are based upon conflicting observational studies describing an increased risk for fractures, ischaemic cardiopathy, and some cancers, with levels above 30 to 48 ng/mL (75 to 120 nmol/L) 167, 172, 173, 174, 175. Based on a recent analysis from the 2007–2010 National Health and Nutrition Examination Survey, proposals for lowering the cut‐off for vitamin D deficiency to 12.5 ng/mL (31.2 nmol/L) have emerged 176.…”