Bone Abstracts

Background: Chronic renal, liver and heart failure in children associate with multiple skeletal complications. Increased fracture incidence often persists after transplantation and might be related to alterations in bone material properties. Moreover, it is not clear whether bisphosphonate therapy (BP) alters bone matrix mineralization in these patients.

Methods: In the present study we evaluated bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) in transiliac bone biopsies obtained from kidney (n=9), liver (n=9) and heart (n=5) transplant recipients (aged 7.6–19.7 years, 6.0±5.6 years post-transplantation) with suspected osteoporosis and in two kidney and four liver recipients after 2 years’ BP treatment (paired biopsies). Furthermore, we related the BMDD parameters with clinical and bone histomorphometric outcomes.

Results: Compared to healthy children, the qBEI analyses in transplant recipients prior BP revealed an increase in the most frequently occurring calcium concentration (+2.9%, P=0.001;+3.5%, P=0.014), in the portion of fully mineralized bone (fivefold; 10-fold, both P<0.0001), in heterogeneity of mineralization (+26,5% and +27.8%, both P<0.0001), in cancellous and cortical bone respectively. Moreover, we observed a strong inverse correlation between the average calcium content of the bone matrix and patients’ biochemical ALP levels, histomorphometric indices of bone formation and resorption. BP did not significantly alter the average mean calcium content of the bone matrix (cancellous bone: 21.6% post BP vs 22.2% prior BP, P=0.47; cortical bone: 21.4% after BP vs 22.0% prior BP, P=0.56) except in one patient with abnormally low bone matrix mineralization and increased indices of bone turnover that normalized after treatment. Accumulation of mineralized cartilage was observed in the bone tissue after BP.

Conclusions: The abnormally high bone matrix mineralization in transplant recipients, consistent with serum and histomorphometric outcomes, indicates a history of low bone turnover with accumulation of fully mineralized bone packets. The increased heterogeneity of mineralization suggests local alterations in mineralization kinetics. This may be linked to dysfunctional osteocytes that accumulate within the bone matrix during organ failure and concomitant glucocorticoid and immunosuppressive medication. BP does not further increase bone matrix mineralization, however the presence of mineralized cartilage warrants further clarifications.

The authors have no conflicts of interest.

Disclosure: The authors declared no competing interests.