A Real-world Study of Denosumab For Reducing Refracture Risk after Percutaneous Vertebral Augmentation

Abstract

Objective: To investigate the use of anti-osteoporotic agents and refracture incidence in patients with osteoporotic vertebral compression fracture (OVCF) following percutaneous vertebral augmentation (PVA) and to evaluate the real-world treatment of patients using denosumab following PVA. This study aims to provide spine surgeons with empirical insights derived from real-world scenarios to enhance the management of bone health in OVCF patients.

Methods: This retrospective cohort study was based on data from the MarketScan and Optum databases from the USA. Female patients aged 55–90 years who underwent PVA for OVCF between January 2013 and March 2020 were included and followed up from the day after surgery. Patients who received at least one dose of denosumab were included in the denosumab cohort and were further divided into the on-treatment and off-treatment groups according to whether they received a second dose of denosumab, with follow-up beginning on the index day (225 days after the first denosumab dose). In this study, the off-treatment group was considered as the control group. Refracture incidence after PVA, the proportion of patients using anti-osteoporotic agents in the total study population, and refracture incidence after the index day in the denosumab cohort were analyzed.

Results: A total of 13,451 and 21,420 patients from the MarketScan and Optum databases, respectively, were included. In the denosumab cohort, the cumulative incidence of clinical osteoporotic fractures within 3 years after the index day was significantly lower in the on-treatment group than in the off-treatment group (MarketScan database: 23.0% vs 39.0%, p = 0.002; Optum database: 28.2% vs 40.0%, p = 0.023). The cumulative incidence of clinical vertebral fractures was also lower in the on-treatment group than in the off-treatment group, with a significant difference in the MarketScan database (14.4% vs 25.5%, p = 0.002) and a numerical difference was found in the Optum database (20.2% vs 27.5%, p = 0.084).The proportion of patients using anti-osteoporotic agents was low at 6 months postoperatively, with only approximately 7% using denosumab and 13%–15% taking oral bisphosphonates.

Conclusion: Postmenopausal women have a high refracture rate and a low proportion of anti-osteoporotic drug use after PVA. Continued denosumab treatment after PVA is associated with a lower risk of osteoporotic and clinical vertebral fractures. Therefore, denosumab may be a treatment option for patients with osteoporosis after PVA.

Keywords

Denosumab / Health claim database / Fracture / Percutaneous vertebral augmentation / Osteoporosis

References

[1] Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update. Endor Pract. 2020; 26(Suppl 1): 1–46.

[2] Bousson V, Hamze B, Odri G, et al. Percutaneous vertebral augmentation techniques in osteoporotic and traumatic fractures. Semin Interevent Radiol. 2018; 35(4): 309–323.

[3] Yang D, Zhang Y, Ma X, Huo L, Li L, Gao Y. Resources utilization and economic burden of percutaneous vertebroplasty or percutaneous kyphoplasty for treatment of osteoporotic vertebral compression fractures in China: a retrospective claim database study. BMC Musculoskelet Disord. 2020; 21(1): 255.

[4] Rabei R, Patel K, Ginsburg M, et al. Percutaneous vertebral augmentation for vertebral compression fractures: national trends in the medicare population (2005-2015). Spine (Phila Pa 1976). 2019; 44(2): 123–133.

[5] Chinese Society of osteoporosis and Bone Mineral Research. Expert consensus on the diagnosis and treatment and management of osteoporotic vertebral compression fractures. Chin J Osteoporosis Bone Miner Res. 2018; 11(5): 425–437.

[6] Dai C, Liang G, Zhang Y, Dong Y, Zhou X. Risk factors of vertebral re-fracture after PVP or PKP for osteoporotic vertebral compression fractures, especially in eastern Asia: a systematic review and meta-analysis. J Orthop Surg Res. 2022; 17(1): 161.

[7] Pang KL, Low NY, Chin KY. A review on the role of denosumab in fracture prevention. Drug Des Devel Ther. 2020; 14: 4029–4051.

[8] Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361(8): 756–765.

[9] Kao FC, Hsu YC, Chen TS, Tu YK, Liu PH. Effects of injected antiosteoporotic medication versus oral bisphosphonates on rates of repeated vertebroplasty or kyphoplasty. Clin Ther. 2020; 42(6): 1087–1098.e2.

[10] Dave CV, Schneeweiss S, Kim D, et al. Sodium-glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections: a population-based cohort study. Ann Intern Med. 2019; 171(4): 248–256.

[11] George MD, Baker JF, Winthrop K, et al. Risk for serious infection with low-dose glucocorticoids in patients with rheumatoid arthritis: a cohort study. Ann Intern Med. 2020; 173(11): 870–878.

[12] Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014; 33(7): 1242–1258.

[13] Kendler DL, Chines A, Brandi ML, et al. The risk of subsequent osteoporotic fractures is decreased in subjects experiencing fracture while on denosumab: results from the FREEDOM and FREEDOM extension studies. Osteoporos Int. 2019; 30(1): 71–78.

[14] McClung MR, Boonen S, Törring O, Roux C, Rizzoli R, Bone HG, et al. Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. J Bone Miner Res. 2012; 27(1): 211–218.

[15] Nakamura T, Matsumoto T, Sugimoto T, et al. Clinical trials express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014; 99(7): 2599–2607.

[16] Wardlaw D, Cummings SR, Van Meirhaeghe J, et al. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet. 2009; 373: 1016–1024.

[17] Clark W, Bird P, Gonski P, Diamond TH, Smerdely P, McNeil HP, et al. Safety and efficacy of vertebroplasty for acute painful osteoporotic fractures (VAPOUR): a multicentre, randomised, double-blind, placebo-controlled trial [published correction appears in Lancet. 2017 Feb 11;389(10069):602]. Lancet. 2016; 388(10052): 1408–1416.

[18] Klazen CA, Lohle PN, de Vries J, et al. Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial. Lancet. 2010; 376(9746): 1085–1092.

[19] Farrokhi MR, Alibai E, Maghami Z. Randomized controlled trial of percutaneous vertebroplasty versus optimal medical management for the relief of pain and disability in acute osteoporotic vertebral compression fractures. J Neurosurg Spine. 2011; 14: 561–569.

[20] Meirhaeghe JV, Bastian L, Boonen S, Ranstam J, Tillman JB, Wardlaw D. A randomized trial of balloon kyphoplasty and nonsurgical management for treating acute vertebral compression fractures. Vertebral body kyphosis correction and surgical parameters. Spine. 2013; 38(12): 971–983.

[21] Boonen S, Van Meirhaeghe J, Bastian L, et al. Balloon kyphoplasty for the treatment of acute vertebral compression fractures: 2-year results from a randomized trial. J Bone Miner Res. 2011; 26: 1627–1637.

[22] Sun HB, Jing XS, Tang H, Hai Y, Li JJ, Shan JL, et al. Clinical and radiological subsequent fractures after vertebral augmentation for treating osteoporotic vertebral compression fractures: a meta-analysis. Eur Spine J. 2020; 29(10): 2576–2590.

[23] Xie W, Jin D, Wan C, Ding J, Zhang S, Jiang X, et al. The incidence of new vertebral fractures following vertebral augmentation: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2015; 94(37): e1532.

[24] Barr JD, Jensen ME, Hirsch JA, McGraw J, Barr RM, Brook AL, et al. Position statement on percutaneous vertebral augmentation: a consensus statement developed by the Society of Interventional Radiology (SIR), American Association of Neurological Surgeons (AANS) and the Congress of Neurological Surgeons (CNS), American College of Radiology (ACR), American Society of Neuroradiology (ASNR), American Society of Spine Radiology (ASSR), Canadian Interventional Radiology Association (CIRA), and the Society of Neuro Interventional Surgery (SNIS). J Vasc Interv Radiol. 2014; 25(2): 171–181.

[25] Palacios S, Kalouche-Khalil L, Rizzoli R, et al. Treatment with denosumab reduces secondary fracture risk in women with postmenopausal osteoporosis. Climacteric. 2015; 18(6): 805–812.

[26] Boonen S, Adachi JD, Man Z, et al. Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab. 2011; 96(6): 1727–1736.

[27] Jamal SA, Ljunggren O, Stehman-Breen C, et al. Effects of denosumab on fracture and bone mineral density by level of kidney function. J Bone Miner Res. 2011; 26(8): 1829–1835.

RIGHTS & PERMISSIONS

2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.