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Contrary to frequent claims, vitamin D insufficiency does not generally cause malabsorption of calcium because serum 1,25(OH)(2)D, which is the major determinant of calcium absorption, is maintained by secondary hyperparathyroidism. Nevertheless, because malabsorption of calcium has been described in osteomalacia, there must be a 25(OH)D level below which the serum 1,25(OH)(2)D can no longer be sustained, although it has never been defined. This paper seeks to define it. We examined the records of 3661 patients and found 319 with a serum 25(OH)D < or = 40 nM, in whom calcium absorption, serum calcium, PTH, bone markers, and vitamin D metabolites had been measured. They were grouped according to their serum 25(OH)D into four categories, 0-10, 11-20, 21-30, and 31-40 nM, and differences between the groups were tested by ANOVA. Correlations between the variables were also examined. Serum calcium, 1,25(OH)(2)D, and calcium absorption were significantly decreased and serum PTH and alkaline phosphatase (ALP) and urine hydroxyproline were increased in those with 25(OH)D < or = 10 nM. Serum ALP and urine hydroxyproline were more strongly related, inversely, to calcium absorption than to the vitamin D metabolites. We conclude that vitamin D deficiency does not reduce serum 1,25(OH)(2)D, and therefore calcium absorption, until the serum 25(OH)D falls to approximately 10 nM. At this level, the substrate concentration seems to be insufficient to maintain the level of the dihydroxy metabolite despite secondary hyperparathyroidism. Further studies are needed to see how these changes correlate with the histological changes of osteomalacia.

The association between increased risk of hip fracture and low vitamin D status has long been recognized. However, the level of vitamin D required to maintain bone strength is controversial. We used a rodent model of vitamin D depletion to quantify the 25-hydroxyvitamin D (25D) levels required for normal mineralization. Six groups of 10-wk-old male Sprague-Dawley rats (n = 42) were fed a diet containing 0.4% calcium and various levels of dietary vitamin D(3) for 4 mo to achieve stable mean serum 25D levels ranging between 10 and 115 nM. At 7 mo of age, animals were killed, and the histomorphometry of distal and proximal femora and L(2) vertebra was analyzed. Total RNA was extracted from whole femora for real-time RT-PCR analyses. In the distal femoral metaphysis, trabecular bone mineral volume (BV/TV) showed a significant positive association with circulating 25D levels (r(2) = 0.42, p < 0.01) in the animals with serum 25D levels between 20 and 115 nM. Osteoclast surface (Oc.S) levels were positively associated with RANKL:OPG mRNA ratio, higher in groups with lower serum 25D levels, and were independent of serum 1,25D levels. Serum 25D levels 80 nM are needed for optimal bone volume. These data indicate that serum 25D levels are a major determinant of osteoclastogenesis and bone mineral volume and are consistent with the levels of 25D recommended to reduce the risk of fracture in humans.

Summary Objective To determine the effects of menopause on bone-related variables in Indonesian women and to compare them with corresponding data in Caucasian Australian women. Design A study of bone-related variables in women aged 45 ‐55 years in Jakarta compared with corresponding historical data from Caucasian Australian women. Measurements Dietary intakes, bone mineral density (BMD) and calcium-related variables in blood and urine. Results Dietary calcium, phosphorus and protein intakes were significantly lower in the women from Jakarta than in those from Adelaide (all P < 0·001), probably because of lower milk consumption, but energy intake was similar in the two cities. Indonesian women were shorter and lighter than Australian women ( P < 0·001) but had a comparable body mass index (BMI). The Indonesians also had a lower spinal BMD than the Australians but this was accounted for by the differences in height and weight between the two populations. The differences in serum and urinary calcium and phosphate and serum alkaline phosphatase across the menopause were comparable in Indonesian and Australian women but creatinine excretion was 25% lower in Jakarta than in Adelaide ( P < 0·001) and this was probably sufficient to account for higher ratios of some urinary solutes to urinary creatinine in the Indonesians. Serum 25-hydroxyvitamin D (25OHD) levels were significantly lower ( P < 0·001) and serum PTH levels significantly higher ( P = 0·0045) in Jakarta than in Adelaide. Conclusions The differences in bone-related biochemical variables across the menopause were similar in the two populations, but calcium and protein intake and urine creatinine were lower in Indonesian than in Australian women. Serum 25OHD was lower and PTH higher in the Indonesian women, probably because of their darker skin, their practice of avoiding direct sunlight and the heavy atmospheric pollution in Jakarta.