Vitamin D insufficiency and deficiency: in search of a bone disease.

The definition of deficiency or insufficiency of vitamin D remains challenging because currently used thresholds of <30 ​nmol/L and between 30 and either 50 or 75 ​nmol/L are not consistently associated with clinical or biochemical abnormalities suggestive of secondary hyperparathyroidism, compromised bone volume, microarchitecture, or osteomalacia. Indeed, there is little convincing clinical, biochemical, bone densitometric, microarchitectural, or histomorphometric evidence that 25-hydroxyvitamin D [25(OH)D] levels between 30 and 75 ​nmol/L in community dwellers identify a vitamin D 'insufficiency' disease. There is evidence of modest elevations of serum parathyroid hormone in a minority of individuals with 25(OH)D level <30 ​nmol/L, alerting to the possibility of a 'deficiency' state. However, even at this level of 'deficiency', most individuals have no biochemical or bone structural abnormalities. Meta-analyses of studies grouped according to commonality in dosage of vitamin D, with or without calcium supplementation, are used to make inferences concerning the correct treatment regimens, but confounders make these inferences problematic. Few well-designed and well-executed placebo-controlled studies have tested the antifracture efficacy and safety of different doses of vitamin D or conducted factorial-designed placebo-controlled trials comparing vitamin D plus calcium supplements versus either drug alone. By contrast, it is likely that there is a vitamin D deficiency state compromising bone health in residents of nursing homes and patients with limited sunlight exposure, malnutrition, or malabsorption. These circumstances signal the possibility of emerging or established bone disease requiring investigation and supplementation if appropriate.