Introduction: Several risk factors are involved in post-liver transplantation osteoporosis. Immunosuppressive agents, glucocorticoids, decreased renal function associated with secondary hyperparathyroidism and immobilization are the main determinants of fragility fractures in this population. Denosumab is highly effective in increasing bone mineral density (BMD) and preventing fragility fractures. However, the efficacy of denosumab in liver transplantation osteoporosis has never been described. The aim of this study was to evaluate bone turnover markers and BMD following denosumab administration in post-liver transplantation osteoporosis.
Subjects and methods: Twenty-nine patients seen at the Endocrinology Unit of Policlinico di SantOrsola, Bologna (7 post-menopausal females and 22 males, mean age 64±8 years) who underwent liver transplantation between 1990 and 2018 were retrospectively evaluated. All patients had multiple fragility fractures, namely, vertebral fractures (with a mean of 3 fractures for each patient), diagnosed both clinically and with morphometry. All started denosumab 60 mg every 6 months between July 2014 up to May 2018 (96±70 months after transplantation). Twenty-eight patients were on calcineurin inhibitors and 6 patients were on 5 mg to 10 mg/day prednisone regimen. All patients were receiving cholecalciferol (mean dose of 1860 IU/day). Four patients had recently terminated teriparatide and ten patients were switched to denosumab from oral bisphosphonates. BMD by dual-energy X-ray absorptiometry (DXA) was measured at baseline and every 18-24 months. Baseline and 6-month bone turnover markers were assessed. All patients had a minimum follow-up period of 6 months.
Results: Denosumab was effective in reducing total (P=0.010) and bone-specific (P=0.007) alkaline phosphatase as well as ß-CTX (P=0.002) at six months after the first administration, regardless of prior bisphosphonate or teriparatide treatment. During follow-up, no significant change in BMD at femoral neck (+0.031 g/cm2; %change 3.4±11.2; P=0.290) or spine (+0.017 g/cm2; %change 5.6±11.5; P=0.355) was observed in a mean follow-up period of 27±10 (range 13-44) months. We found a slight but significant increase of total hip BMD (+0.033 g/cm2; %change 6.1±7.0; P=0.045). One atraumatic compound diaphyseal femoral fracture was observed in a diabetic male patient naïve to any osteoporotic treatments, 14 months after starting denosumab. No further clinical fractures were reported in our study population.
Conclusion: Denosumab is highly effective in reducing bone turnover markers in post-liver transplantation osteoporosis. Only mild total hip BMD gain was observed during the period of observation. A longer follow-up is needed to confirm this apparently blunted response.
18 - 21 May 2019
European Society of Endocrinology