Effects of denosumab versus teriparatide in glucocorticoid-induced osteoporosis patients with prior bisphosphonate treatment

Abstract

Introduction Osteoporosis is one of the serious adverse effects associated with glucocorticoid therapy. Although bisphosphonates have been used for glucocorticoid-induced osteoporosis (GIO), some patients have shown an inadequate response. In such cases, denosumab or teriparatide are used. However, there is no consensus on which of these two drugs is superior. We prospectively compared denosumab's and teriparatide's effects on the bone mineral density (BMD) in GIO patients with prior bisphosphonate treatment. Materials and methods After receiving oral bisphosphonates for ≥2 years, GIO patients with low T-score BMD (<−2.5) were switched from bisphosphonates to denosumab (n = 20) or daily teriparatide (n = 21). We measured the BMD (lumbar spine, femoral neck, and total hip) in both groups every 6 months for 24 months. Results At 24 months of treatment, the lumbar spine BMD increased significantly from baseline in both the denosumab and teriparatide groups (baseline vs. denosumab and teriparatide; 5.9 ± 5.6%, P < 0.001 and 7.9 ± 5.4%, P < 0.001). A significant increase in femoral neck BMD from baseline occurred only in the teriparatide group (6.6 ± 10.8%, P < 0.05); denosumab (1.5 ± 5.0%). No significant changes occurred in the total hip BMD from baseline in either group (−0.1 ± 5.6% and 3.3 ± 7.5%, respectively). There was no significant difference between the denosumab and teriparatide groups at 24 months in lumbar spine and femoral neck BMD, but was significantly higher in the teriparatide group at 12 months (P < 0.01 and P < 0.05 in the lumbar spine and femoral neck, respectively). Conclusion Teriparatide might have some advantages over denosumab and be a good alternative for treating GIO patients with prior bisphosphonate treatment.

Four-Year Teriparatide Followed by Denosumab vs. Continuous Denosumab in Glucocorticoid-Induced Osteoporosis Patients With Prior Bisphosphonate Treatment

“…In the DATA extension study, which was conducted in bisphosphonate-naïve women with postmenopausal osteoporosis, both the denosumab- and teriparatide-treated groups showed significant increases from baseline in BMD at the lumbar spine, femoral neck, and total hip, with no significant differences between the two groups ( 14 ). On the other hand, our earlier study demonstrated that teriparatide has some advantages over denosumab in GIO patients with prior bisphosphonate treatment ( 15 ). The discrepancy in the results may be due to the different backgrounds of the patients addressed in each study.…”

“…This study was conducted from 2014 to 2021 at Kindai University Hospital (Osaka, Japan). The original study ( 15 ) was a 24-month, prospective, open-label, non-randomized clinical trial. The present study’s inclusion and exclusion criteria were the same as those of the original study.…”

“…The efficacy of this sequential treatment has not been well studied in GIO. In the present 4-year study, we extended our 2-year study ( 15 ) and compared a treatment group that transitioned from teriparatide to denosumab with a treatment group that continued denosumab for 4 years. We investigated whether the teriparatide advantage gained in the first 2 years would be maintained in the subsequent 2 years.…”

The molecular etiology and treatment of glucocorticoid-induced osteoporosis

“…Teriparatide is an active form of parathyroid hormone (PTH) consisting of the N-terminal 34 amino acids. In the clinical survey, teriparatide significantly increases the expression of bone formation markers and bone mass density of GIOP patients [ 159 160 161 ]. Intermittent use of teriparatide facilitates osteoblast production, increases TNAP activity [ 162 ], and promotes WNT signaling by reducing WNT signaling inhibitors, such as Sost , Dkk1 , sFRP-1 , and axin-2 [ 49 163 164 165 ].…”

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

“…However, due to off-target and other side effects, these drugs are far from satisfactory in use ( Whittier and Saag, 2016 ; Chotiyarnwong and McCloskey, 2020 ). For example, gastrointestinal discomfort was often found in the patients with oral bisphosphonates, meanwhile, mandible osteonecrosis, nephrotoxicity, and the increased risk of venous thrombosis were also found in the patients with intravenous bisphosphonates ( Cummings et al, 2009 ; Hirooka et al, 2020 ). Therefore, there is an urgent clinical need for a new effective treatment strategy for GIOP treatment.…”