Chronic calcium- and vitamin-D-deficiencies are crucial risk factors for osteoporosis. However, their significance for fracture healing is still poorly investigated, despite the clinical evidence that osteoporotic bone healing is disturbed. This study addressed the important question, whether chronic deprivation of calcium and vitamin D compromises bone repair and if this could be rescued by a supplementation post-trauma. Because clinical hints suggest that a fracture induces general bone loss in the skeleton, thus further increasing fracture risk, we also analyzed, if a fracture induces bone loss particularly under deficiency conditions and if this can be prevented by a specific supplementation therapy.
Female C57BL/6J mice were ovarectomized to induce an osteoporotic phenotype. One group was fed a standard-diet and second group a calcium/vitamin-D-deficient-diet. After 8 weeks, all mice received a femur osteotomy. Half of the group with chronic calcium/vitamin-D-deficiency was supplemented with calcium/vitamin-D post-trauma. Bone healing and the general bone status were assessed at day 10 and 23 by biomechanical analysis, μCT, histomorphometry and serum analysis. To evaluate posttraumatic bone turnover, intact skeleton of fractured mice was compared to non-fractured mice. n=410; P<0.05; ANOVA/LSD.
Calcium/vitamin-D-deficiency impaired fracture healing as confirmed by significantly decreased bone content in the fracture callus (−18%). Furthermore, fractured mice of the deficient-group exhibited significantly more osteoclasts in the callus and intact skeleton compared to standard-group or non-fractured mice, respectively, indicating posttraumatic bone loss. Calcium/vitamin-D-supplementation abolished the negative effects as demonstrated by significantly improved bone formation and reduced osteoclast activity. In the serum, FGF-23 was increased and CTX was decreased (P<0.05).
Calcium/vitamin-D-deficiency disturbed osteoporotic fracture healing accompanied by increased osteoclast activity. Supplementation abolished these effects possibly mediated through FGF-23 that was already shown to inhibit osteoclast formation. The results support the therapeutic potential for calcium/vitamin-D-supplementation to enhance osteoporotic fracture healing and prevent posttraumatic bone loss in the clinics.
14 May 2016 - 17 May 2016