Background/Purpose: The efficacies of switching bisphosphonate (BP) to denosumab (DMAb), an anti-RANKL antibody which strongly inhibits bone resorption, or daily teriparatide (TPTD), a bone anabolic agent which induce bone formation, has been reported in primary osteoporosis. However, its adaptation and efficacies in patients with rheumatoid arthritis (RA) still lack reliable evidence and also no previous reports directly compared the results of these two switching treatments.

Methods: 194 patients with RA treated by BP [177 female, 65.9 years old, disease duration 17.8 years, RF positivity 77.8%, DAS28-CRP 2.3, 75.8% with oral prednisolone (PSL) 3.6mg/day, 23.2% with biologics, prior BP duration 40.0 months, prior vertebral fracture rate 41.8%, T-scores: lumbar spine (LS) -1.8, femoral neck (FN) -2.3, total hip (TH) -2.0] were allocated to either the (1) BP-continued group (BP; n=80), (2) switched-to-DMAb group (DMAb; n=74), or (3) switched-to-TPTD group (TPTD; n=40) based on each physicians’ decision and followed up for 12 months by monitoring bone mineral density (BMD), trabecular bone score (TBS), bone turnover markers, and fracture incidence.

Results: At baseline, TPTD group showed significantly lower T-scores than BP group in all resions (P<0.05), while no significant differences were observed between DMAb and BP group, and DMAb and TPTD group. Changes of BMD from baseline→6→12 months were as follows. (1) BP group: LS; 0→1.1→2.5％, TH; 0→0.3→0.2％, FN; 0→0.5→0.8％, (2) DMAb group: LS; 0→2.8→4.9％, TH; 0→1.5→3.0％, FN; 0→2.0→3.9％, (3) TPTD group: LS; 0→4.2→6.0％, TH; 0→-1.4→1.4％, FN; 0→-1.1→2.1％. TBS changed from baseline to 12 months as follows. (1) BP group: -1.4％, (2) DMAb group: 0.4％, (3) TPTD group: 2.7％. DMAb group showed significant increase in LS, TH, and FN BMD (P<0.01) and maintained TBS (P<0.01) compared to BP group at 12 months, and TPTD group showed significant increase in LS BMD (P<0.01) and TBS (P<0.001) compared to BP group at 12 months. TPTD group showed similar increase in LS, TH, and FN BMD, while significantly increased TBS (P<0.05) compared to DMAb group at 12 months. Changes of bone turnover markers were as follows. (1) BP group: bone resorption marker, TRACP-5b; 0→-3.5→1.4％, bone formation marker, PINP; 0→-9.6→-13.4％, (2) DMAb group: TRACP-5b; 0→-28.5→-27.9％, PINP; 0→-14.5→-17.6％, (3) TPTD group: TRACP-5b; 0→77.1→77.6％, PINP; 0→296.5→227.7％. DMAb group showed significant decrease in TRACP-5b (P<0.001), and TPTD group showed significant increase in TRACP-5b and PINP (P<0.001) compared to BP and DMAb group at 12 months. The fracture incidence during this period was (1) BP group: 3.8% (1 vertebra, 1 forearm, and 1 humerus), (2) DMAb group: 1.4% (1 rib), (3) TPTD group: 2.5% (1 toe). DMAb and TPTD group showed no major fractures during this period.

Conclusion: Switching oral BP to DMAb significantly increased LS, TH, and FN BMD, and decreased TRACP-5b, while switching to TPTD increased LS BMD, TBS, and total bone turnover at most compared to continuing BP at 12 months. Our results indicate that switching BP to DMAb or TPTD by determining treatment target may provide useful treatment option in RA associated osteoporosis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/assessment-of-the-effects-of-switching-bisphosphonates-to-denosumab-or-daily-teriparatide-in-patients-with-rheumatoid-arthritis/