Background/Purpose: In osteoporotic patients, discontinuation of denosumab is associated with a rapid increase in bone turnover and bone loss. Denosumab was recently proven to have clear structure modifying effects in erosive hand osteoarthritis (OA) patients compared to placebo. So far, the effect of denosumab discontinuation in a non-osteoporotic population is unclear. The objective was to investigate whether buffered soluble alendronate after denosumab discontinuation, can counter potential increase in bone turnover in this non-osteoporotic population.

Methods: Patients with erosive hand OA, who participated in a RCT with denosumab, were randomized to open label treatment with oral effervescent alendronate 70 mg weekly for either 24 or 48 weeks, after discontinuating denosumab treatment. Underlying osteoporosis was excluded at baseline. Serum bone turnover markers (C-terminal telopeptide of type I collagen (CTx-I) and N-terminal propeptide of type I procollagen (PINP) were measured at baseline, week 12, week 24 and week 48. Dual energy X-ray absorptiometry was performed at baseline, week 24 and week 48. The primary end point was the number of patients maintaining serum bone turnover markers within pre-menopausal reference range. Statistical analysis was performed with an intention to treat approach. Secondary end point was change in bone mineral density (BMD). Occurrence of adverse events were recorded.

Results: Fifteen patients were randomized to each treatment group. At week 48, 5 of 15 (33%) patients from alendronate 24 weeks vs 1 of 15 (7%) from alendronate 48 weeks, showed CTx-I values above pre-menopausal ranges. For PINP, 7 of 15 (47%) from alendronate 24 weeks vs. 2 of 15 (13%) from alendronate 48 weeks, showed values exceeding pre-menopausal ranges. The amount of patients above pre-menopausal ranges was not significantly different between both groups (p=0.11 and p=0.17 for CTx-I and PINP respectively). Mean changes of CTx-I levels between baseline and week 48 were significantly lower for alendronate 48 vs 24 weeks (p=0.043). For PINP, mean changes were numerically lower in alendronate 48 weeks but not statistically significant. BMD T-scores did not differ significantly between baseline and week 48, except for T-scores at the lumbar spine in alendronate 24 weeks. No significant differences were seen in mean change BMD between treatment groups. No fractures were reported.

Conclusion: Soluble alendronate 70mg weekly after denosumab discontinuation in this non-osteoporotic population did not maintain bone turnover markers under premenopausal reference range in all patients. Clinical implications of the increase of bone turnover markers in this non osteoporotic remain doubtful, since BMD values did not change over time, except at the lumbar spine in the 24 weeks alendronate group. Longer follow-up is warranted to evaluate clinical consequences on long term.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/soluble-buffered-alendronate-after-denosumab-discontinuation-in-erosive-hand-oa-patients/