The comparative efficiency of denosumab treatment in patients with postmenopausal osteoporosis, primary hyperparathyroidism and glucocorticoid-induced osteoporosis in real clinical practice

Background: Denosumab is a highly effective and safe first-line treatment for osteoporosis. Primary hyperparathyroidism is a prevalent condition found in patients with osteoporosis. However, data regarding effectiveness of denosumab treatment in patients with PHPT are scarce.

Aims: To estimate the comparative effects of denosumab to treat postmenopausal osteoporosis (PMO) and osteoporosis caused by primary hyperparathyroidism (PHPT) or glucocorticoid-induced osteoporosis (GIOP) in postmenopausal women in routine clinical practice. Materials and methods: Retrospective study based on the medical card records. Patients over 50 years of age with verified osteoporosis (based on bone mineral density (BMD) T-score ≤ -2.5 SD and/or low-trauma fracture), who had at least 3 denosumab injections were included in the study.

Results: 162 patients were included and divided into three groups according to the etiology of osteoporosis. The first group consisted of postmenopausal women with osteoporosis (PMO) [(n=85); median age 70 [64;78]]. Patients with glucocorticoid-induced osteoporosis (GIOP) were enrolled in the second group [(n=16); male to female ratio =1:15; median age 60 [57,8; 66,3]]. The third group consisted of patients with PHPT and osteoporosis [(n=61); male to female=2:59; median age 68 [63; 75]]. Among all patients, denosumab treatment significantly increased BMD and decreased serum levels of calcium and CTx compared with baseline. PMO: the median increase in BMD according to the T-score was L1-L4 0,6 (p<0,001), femoral neck 0,2 (p<0,001); serum calcium -0,04 (p=0,004). PHPT: the median increase in BMD according to the T-score was L1-L4 0,6 (p<0,001), femoral neck 0,2 (p<0,001); radius 33% 0,25 (p=0,002), serum calcium -0,04 (p<0,001). In patients with GIOP, denosumab increased BMD in the lumbar spine L1-L4 0,5 (p=0,004). There was no difference in BMD increase or in levels of bone turnover suppression between the groups. A marked decline in levels of serum calcium was noted among patients with GFR less than 60 ml / min / 1.73 m2 (median Δ Са serum=0,24 p<0,001), compared to patients without CKD (median Δ Са serum=0,08 p<0,001).

Conclusion: Denosumab treatment is similarly effective for increasing BMD and decreasing bone turnover markers in patients with PMO and PHPT among postmenopausal women. The hypocalciemic effect of denosumab is most significant in subjects with PHPT.

1. Belaya ZE, Rozhinskaya LY. Novye napravleniya v terapii osteoporoza - primenenie monoklonal’nykh chelovecheskikh antitel k RANKL (denosumab). Osteoporosis and Bone Diseases. 2011;14(2):23-26. (In Russ.)] doi: https://doi.org/10.14341/osteo2011223-26.

2. Reid IR, Miller PD, Brown JP, et al. Effects of denosumab on bone histomorphometry: The FREEDOM and STAND studies. J. Bone Miner. Res. 2010;25(10):2256-2265. doi: https://doi.org/10.1002/jbmr.149.

3. Seeman E, Delmas PD, Hanley DA, et al. Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate. J. Bone Miner. Res. 2010;25(8):1886-1894. doi: https://doi.org/10.1002/jbmr.81.

4. Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. The Lancet Diabetes & Endocrinology. 2017;5(7):513-523. doi: https://doi.org/10.1016/s2213-8587(17)30138-9.

5. Brown JP, Roux C, Ho PR, et al. Denosumab significantly increases bone mineral density and reduces bone turnover compared with monthly oral ibandronate and risedronate in postmenopausal women who remained at higher risk for fracture despite previous suboptimal treatment with an oral bisphosphonate. Osteoporos. Int. 2014. doi: https://doi.org/10.1007/s00198-014-2692-7.

6. Smith MR, Saad F, Egerdie B, et al. Effects of Denosumab on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer. J. Urol. 2009;182(6):2670-2676. doi: https://doi.org/10.1016/j.juro.2009.08.048.

7. Ellis GK, Bone HG, Chlebowski R, et al. Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study. Breast Cancer Res. Treat. 2009;118(1):81-87. doi: https://doi.org/10.1007/s10549-009-0352-y.

8. Gu H-F, Gu L-J, Wu Y, et al. Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis. Medicine. 2015;94(44):e1674. doi: https://doi.org/10.1097/md.0000000000001674.

9. Lundgren E, Rastad J, Thurfjell E, et al. Population-based screening for primary hyperparathyroidism with serum calcium and parathyroid hormone values in menopausal women. Surgery. 1997;121(3):287-294. doi: https://doi.org/10.1016/s0039-6060(97)90357-3.

10. Yanbeiy ZA, Hansen KE. Denosumab in the treatment of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis. Drug Des. Devel. Ther. 2019;Volume 13:2843-2852. doi: https://doi.org/10.2147/dddt.s148654.

11. Lyu H, Jundi B, Xu C, et al. Comparison of Denosumab and Bisphosphonates in Patients With Osteoporosis: A MetaAnalysis of Randomized Controlled Trials. J. Clin. Endocr. Metab. 2019;104(5):1753-1765. doi: https://doi.org/10.1210/jc.2018-02236.

12. Leder BZ, Tsai JN, Uihlein AV, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. The Lancet. 2015;386(9999):1147-1155. doi: https://doi.org/10.1016/s0140-6736(15)61120-5.

13. Nitta K, Yajima A, Tsuchiya K. Management of Osteoporosis in Chronic Kidney Disease. Intern. Med. 2017;56(24):3271-3276. doi: https://doi.org/10.2169/internalmedicine.8618-16.

14. Kanis JA, Cooper C, Rizzoli R, Reginster JY. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos. Int. 2018;30(1):3-44. doi: https://doi.org/10.1007/s00198-018-4704-5.

15. Dydykina IS, Kovalenko PS, Smirnov AV, et al. Experience with denosumab therapy for osteoporosis in rheumatoid arthritis patients receiving glucocorticoids. Modern Rheumatology Journal. 2018;12(2):50-57. (In Russ.)] doi: https://doi.org/10.14412/1996-7012-2018-2-50-57.

16. Toropcova NV, Nikitskaya OA, Korotkova TA, Demin NV. Application of recombinant denosumab preparation in women with postmenopausal osteoporosis: two-year study in clinical practice. Lvrach Medical Journal. 2017; №4.

17. Saag KG, Pannacciulli N, Geusens P, et al. Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐ Dummy Trial. Arthritis & Rheumatology. 2019;71(7):1174-1184. doi: https://doi.org/10.1002/art.40874.

18. Eller-Vainicher C, Palmieri S, Cairoli E, et al. Protective Effect of Denosumab on Bone in Older Women with Primary Hyperparathyroidism. J. Am. Geriatr. Soc. 2018;66(3):518-524. doi: https://doi.org/10.1111/jgs.15250.

19. Belaya ZE, Bilezikian JP, Ershova OB, et al. Long-term treatment options for postmenopausal osteoporosis: results of recent clinical studies of Denosumab. Osteoporosis and Bone Diseases. 2018;21(1):17-22. (In Russ.)] doi: https://doi.org/10.14341/osteo9760.

20. Pigarova EA. Prolia (Denosumab): Review of the Latest Publications of American Society of Bone and Mineral Research (Asmbr) in 2014. Osteoporosis and Bone Diseases. 2014;17(3):38-39. (In Russ.)] doi: https://doi.org/10.14341/osteo2014338-39.

21. Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nature Reviews Endocrinology. 2017;14(2):115-125. doi: https://doi.org/10.1038/nrendo.2017.104.

22. Leere JS, Karmisholt J, Robaczyk M, Vestergaard P. Contemporary Medical Management of Primary Hyperparathyroidism: A Systematic Review. Front. Endocrinol. (Lausanne). 2017;8. doi: https://doi.org/10.3389/fendo.2017.00079.

23. Zanocco KA, Yeh MW. Primary Hyperparathyroidism. Endocrinol. Metab. Clin. North Am. 2017;46(1):87-104. doi: https://doi.org/10.1016/j.ecl.2016.09.012.