Bone effects of vitamin D vary by calcium status
MedWire News: Vitamin D exerts opposing effects on bone mineralization depending on serum calcium levels, a study in mice suggests.
The findings indicate that the maintenance of normocalcemia "has priority over skeletal integrity," and that vitamin D not only increases calcium release from bone but also inhibits calcium incorporation in bone.
The study, which was led by Geert Carmeliet (Katholieke Universiteit Leuven, Belgium), aimed to elucidate how bone responds to variations in dietary calcium intake and hence vitamin D-mediated intestinal calcium absorption.
"Insight into these issues is important for correct administration of calcium and vitamin D supplements," note Carmeliet and colleagues in the Journal of Clinical Investigation.
The team developed knockout mice that lacked either the intestinal vitamin D receptor (Vdrint-), or the systemic and osteocyte-specific receptor (Vdr-/-), and compared them with wild-type mice.
As expected, Vdrint- mice showed a reduction in active intestinal calcium absorption, yet their serum calcium levels were normal. This contrasts with Vdr-/- mice, which were hypocalcemic, suggesting that Vdrint- mice can "balance the reduced calcium absorption by compensatory mechanisms," say the authors.
To investigate further they assessed bone homeostasis in the Vdrint- mice, finding that impaired calcium absorption reduced the accrual of bone mass, causing the bones to become fragile and prone to fracture. However, bone growth per se was unaffected.
Subsequent studies of Vdrint- mice showed that normocalcemia was maintained via an upregulation in bone turnover; that impaired mineralization contributed to reduced skeletal calcium content; and that increased skeletal Vdr signaling suppressed skeletal calcium incorporation. In addition, increased circulating levels of active vitamin D impaired mineralization by upregulation the expression of "mineralization inhibitors" such as pyrophosphates.
"Thus, while vitamin D is important for maintaining serum calcium levels, it can also promote bone density loss," the authors summarize.
They say their findings could help findings from clinical trials whereby - contrary to predictions - vitamin D supplementation had either a neutral or negative impact on fracture risk in elderly individuals.
"Conservation of normocalcemia is thus preferred over calcium storage in bone, a finding that should be kept in mind in the prevention and treatment of osteoporosis," Carmeliet and co-authors conclude.
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By Joanna Lyford