Animal models fed low calcium diets demonstrate a negative calcium balance and gross bone loss while the combination of calcium deficiency and oophorectomy enhances overall bone loss. Following oophorectomy the dietary calcium intake required to remain in balance increases some 5 fold, estimated to be approximately 1.3% dietary calcium. In the context of vitamin D and dietary calcium depletion, osteomalacia occurs only when low dietary calcium levels are combined with low vitamin D levels and osteoporosis occurs with either a low level of dietary calcium with adequate vitamin D status or when vitamin D status is low in the presence of adequate dietary calcium intake. Maximum bone architecture and strength is only achieved when an adequate vitamin D status is combined with sufficient dietary calcium to achieve a positive calcium balance. This anabolic effect occurs without a change to intestinal calcium absorption, suggesting dietary calcium and vitamin D have activities in addition to promoting a positive calcium balance. Each of the major bone cell types, osteoblasts, osteoclasts and osteocytes are capable of metabolizing 25 hydroxyvitamin D (25D) to 1,25 dihydroxyvitamin D (1,25D) to elicit biological activities including reduction of bone resorption by osteoclasts and to enhance maturation and mineralization by osteoblasts and osteocytes. Each of these activities is consistent with the actions of adequate circulating levels of 25D observed in vivo.
References
[1]
Bauer, W.; Aub, J.C.; Albright, F. Studies of calcium and phosphorus metabolism. V. A study of the bone trabeculae as a readily available reserve supply of calcium. J. Exp. Med.？1929, 49, 145–162. and references therein.
[2]
Hodgkinson, A.; Aaron, J.E.; Horsman, A.; McLachlan, M.S.; Nordin, B.E. Effect of oophorectomy and calcium deprivation on bone mass in the rat. Clin. Sci. Mol. Med.？1978, 54, 439–446.
[3]
Shen, V.; Birchman, R.; Xu, R.; Lindsay, R.; Dempster, D.W. Short-term changes in histomormorphometric and biochemical turnover markers and bone mineral density in estrogen—and/or dietary calcium—deficient rats. Bone？1995, 16, 149–156.
[4]
O’Loughlin, P.D.; Morris, H.A. Oestrogen deficiency impairs intestinal calcium absorption in the rat. J. Physiol. (Lond.)？1998, 511, 313–322, doi:10.1111/j.1469-7793.1998.313bi.x. 9679184
[5]
Baldock, P.A.J.; Morris, H.A.; Moore, R.J.; Need, A.G.; Durbridge, T.C. Pre-pubertal oophorectomy limits accumulation of cancellous bone in the femur of growing rats with long term effects on metaphyseal architecture. Calcif. Tissue Int.？1998, 62, 244–249.
[6]
Sims, N.A.; Morris, H.A.; Moore, R.J.; Durbridge, T.C. Increased bone resorption precedes bone formation in the ovariectomised rat. Calcif. Tissue Int.？1996, 59, 121–127.
[7]
Mundy, G.R. Osteoporosis and inflammation. Nutr. Rev.？2007, 65, 5147–5151.
[8]
Baldock, P.A.J.; Morris, H.A.; Need, A.G.; Moore, R.J.; Durbridge, T.C. Variation in the short-term changes in bone cell activity immediately following ovariectomy in three regions of the distal femur. J. Bone Miner. Res.？1998, 13, 1451–1457.
[9]
Baldock, P.A.J.; Need, A.G.; Moore, R.J.; Durbridge, T.C.; Morris, H.A. Discordance between bone turnover and bone loss: effects of aging and ovariectomy in the rat. J. Bone Miner. Res.？1999, 14, 1442–1448.
[10]
Baldock, P.A.J. Regional variation in oophorectomy-induced trabecular bone osteopenia in the distal femur of the rat. Ph.D. Thesis, University of Adelaide, Australia, 2001.
[11]
Morris, H.A.; Moore, A.J.; Moore, R.J.; Need, A.G.; O’Loughlin, P.D.; Nordin, C.; Anderson, P.H. Dietary calcium and oestradiol protect osteocyte density and bone structure against the effects of ovariectomy. Bone？2009, 44, S61.
[12]
Underwood, J.L.; DeLuca, H.F. Vitamin D is not directly necessary for bone growth and mineralization. Am. J. Physiol.？1984, 246, E493–E498.
[13]
Baker, M.R.; McDonnell, H.; Peacock, M.; Nordin, B.E. Plasma 25-hydroxy vitamin D concentrations in patients with fractures of the femoral neck. Br. Med. J.？1979, 1, 589.
[14]
Morris, H.A.; Morrison, G.W.; Burr, M.; Thomas, D.W.; Nordin, B.E.C. Vitamin D and femoral neck fractures in elderly South Australia women. Med. J. Aust.？1984, 140, 519–521.
[15]
Bischoff-Ferrari, H.A.; Dietrich, T.; Orav, E.J.; Dawson-Hughes, B. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am. J. Med.？2004, 116, 634–639.
[16]
Anderson, P.H.; Iida, S.; Tyson, J.H.; Turner, A.G.; Morris, H.A. Bone CYP27B1 gene expression is increased with high dietary calcium in mineralising osteoblasts. J. Steroid Biochem. Mol. Biol.？2010, 121, 71–75.
[17]
Weinstein, R.S.; Underwood, J.L.; Hutson, M.S.; DeLuca, H.F. Bone histomorphometry in vitamin D-deficient rats infused with calcium and phosphorus. Am. J. Physiol.？1984, 246, E499–E505.
[18]
Amling, M.; Priemel, M.; Holzmann, T.; Chapin, K.; Rueger, J.M.; Baron, R.; Demay, M.B. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology？1999, 140, 4982–4987.
[19]
Panda, D.K.; Miao, D.; Tremblay, M.L.; Sirois, J.; Farookhi, R.; Hendy, G.N.; Goltzman, D. Targeted ablation of the 25-hydroxyvitamin D 1alpha-hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc. Natl. Acad. Sci. USA？2001, 98, 7498–7503.
[20]
Bischoff-Ferrari, H.A.; Willett, W.C.; Wong, J.B.; Giovannucci, E.; Dietrich, T.; Dawson-Hughes, B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA？2005, 293, 2257–2264.
[21]
Anderson, P.H.; Sawyer, R.K.; Moore, A.J.; May, B.K.; O’Loughlin, P.D.; Morris, H.A. Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J. Bone Miner. Res.？2008, 23, 1789–1797.
[22]
Atkins, G.F.; Anderson, P.H.; Findlay, D.M.; Welldon, K.J.; Vincent, C.; Zannetino, A.C.W.; O’Loughlin, P.D.; Morris, H.A. Metabolism of vitamin D3 in human osteoblasts: evidence for autocrine or paracrine activities of 1α,25-dihydroxyvitamin D3. Bone？2007, 40, 1517–1528.
[23]
Kogawa, M.; Anderson, P.H.; Findlay, D.M.; Morris, H.A.; Atkins, G.J. The metabolism of 25(OH)-vitamin D3 by osteoclasts and their precursors regulates the differentiation of osteoclasts. J. Steroid Biochem. Mol. Biol.？2010, 121, 277–280.
[24]
Tang, W.-J.; Wang, L.-F.; Xu, X.-Y.; Zhou, Y.; Jin, W.-F.; Wang, H.-F.; Gao, J. Autocrine/paracrine action of vitamin D on FGF23 expression in cultured rat osteoblasts. Calcif. Tissue Int.？2010, 86, 404–410.
