Background: Denosumab is a monoclonal antibody against RANK ligand used for the treatment of osteoporosis. Although clinical trials demonstrate that denosumab is highly effective at reducing fragility fractures in postmenopausal osteoporosis, there have been few studies looking at real world outcomes. Our primary aim was to assess the efficacy of denosumab in practice.
Methods: We retrospectively formed a database of 257 patients seen in endocrinology outpatient clinics who have commenced denosumab for the treatment of osteoporosis between January 2011 and January 2018. Data were collected using standardised proforma including demographics, co-morbidities, bone mineral density (BMD), fractures, hospitalisations and biochemistry.
Results: There was a clear female preponderance (95% of patients), mean age at commencement was 75 years. 80% had post-menopausal osteoporosis, with a mean follow-up of 5 injections. Mean CTX at baseline was 0.37 ug/l, at 3 months the mean was 0.09 ug/l, with a mean 70% reduction in CTX. 91.2% had a CTX reduction >50% from baseline or below the lower limit of normal. Similar results were seen for P1NP with 80% of patients having a P1NP fall by >50% baseline or below the lower limit of normal. Mean baseline spine BMD was 0.826 g/cm2, with a mean T-score of −2.9. Mean baseline hip BMD was 0.692 g/cm2 (mean T-score −2.6). 38% patients had at least one repeat DXA. Spine BMD increased by a mean of 4.7%, 79% had stable or improved BMD 23 years after baseline. Similar results were seen for hip BMD, with a mean increase of 2.2 and 81% had stable or better hip BMD, 23 years after baseline scan. 18% had at least one episode of hypocalcaemia, 20% had at least one episode of vitamin D deficiency. 12.5% were hospitalised for infection, the majority (58.3%)chest related. 10.6% had a fracture related admission, the majority were femoral fractures (29%). The average time to fracture after commencing denosumab was 24 months. 23% patients reported complications, though the majority were episodes of hypocalcaemia or infection. <1% patients had osteonecrosis of the jaw and an incidence of 1.6% who had sub-trochanteric fractures. Denosumab was discontinued in 10% of patients, a further 5% of patients had denosumab inadvertently stopped or delayed.
Conclusion: Denosumab is highly effective at reducing biochemical bone turnover markers and improves BMD in the vast majority of patients, in the real-world setting. However, incidences of biochemical hypocalcaemia were high, as were discontinuation rates, with implications for future re-fracture rates.
18 - 21 May 2019
European Society of Endocrinology