Efficacy of bisphosphonate therapy on postmenopausal osteoporotic women with and without diabetes: a prospective trial

Jinyoung Kim, Kyoung Min Kim, Soo Lim, Moo-Il Kang, Ki-Hyun Baek, Yong-Ki Min, Jinyoung Kim, Kyoung Min Kim, Soo Lim, Moo-Il Kang, Ki-Hyun Baek, Yong-Ki Min

Abstract

Background: The co-occurrence of diabetes and osteoporosis is common in postmenopausal women. For the treatment of postmenopausal osteoporosis, current guidelines recommend initial treatment with bisphosphonates, but it is unclear whether bisphosphonates provide a similar degree of therapeutic efficacy in patients with diabetes. This study sought to compare the efficacy of monthly oral ibandronate for retaining bone mineral density (BMD) in diabetic and non-diabetic postmenopausal women with osteoporosis.

Methods: Postmenopausal osteoporotic women with or without diabetes were enrolled in this study from three hospitals in an open-label approach from 2018 to 2020. Each group of patients received oral ibandronate 150 mg once monthly for 1 year. BMD, trabecular bone score (TBS), serum C-terminal telopeptide of type I collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) were evaluated prospectively. Treatment-emergent adverse events and changes in glucose metabolism during drug use were also monitored.

Results: Among the 120 study participants, 104 (86.7%) completed the study. Following 1 year of treatment, BMD increased by 3.41% vs. 3.71% in the lumbar spine, 1.30% vs. 1.18% in the femur neck, and 1.51% vs. 1.58% in the total hip in the non-diabetes and diabetes groups, respectively. There were no significant differences in BMD changes between the groups, and the differences in CTx or P1NP changes between groups were not significant. We did not observe any significant differences in baseline TBS values or the degree of change between before and after 1 year of ibandronate treatment in either group in this study. A total of 11 adverse events (9.2%) that recovered without sequelae occurred among the 120 included patients, and there was no significant difference in the frequency of adverse events between the groups (p = 0.862). The changes in fasting glucose and glycated hemoglobin levels between before and after treatment were not significant in the diabetic group.

Conclusions: Bisphosphonate therapy showed similar increases in BMD and decreases in CTx and P1NP of postmenopausal women with and without diabetes. Monthly oral ibandronate can be a safe and effective therapeutic option in postmenopausal osteoporosis patients with type 2 diabetes.

Trial registration: NCT number: NCT05266261, Date of registration: 04 March 2022.

Keywords: Bisphosphonates; Osteoporosis; Type 2 diabetes mellitus.

Conflict of interest statement

The funder had no role in data collection, analysis, or preparation of the manuscript. The authors have no other conflicts of interest to declare.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Patient follow-up
Fig. 2
Fig. 2
Percentage change in dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck, presented as least square mean and 95% confidence interval. (n = 120, biologically independent samples; 63 for nondiabetes and 57 for diabetes)
Fig. 3
Fig. 3
Percentage change in bone turnover markers presented as adjusted mean and 95% confidence interval using the generalized estimating equations for repeated measures analysis. (n = 76, biologically independent samples; 27 for nondiabetes and 49 for diabetes)

References

    1. Paschou SA, Dede AD, Anagnostis PG, Vryonidou A, Morganstein D, Goulis DG. Type 2 diabetes and osteoporosis: A guide to optimal management. J Clin Endocrinol Metab. 2017;102(10):3621–3634. doi: 10.1210/jc.2017-00042.
    1. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318(20):1315–1321. doi: 10.1056/NEJM198805193182007.
    1. Kusumbe AP, Ramasamy SK, Adams RH. Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature. 2014;507(7492):323–328. doi: 10.1038/nature13145.
    1. Schwartz AV. Diabetes mellitus: does it affect bone? Calcif Tissue Int. 2003;73(6):515–519. doi: 10.1007/s00223-003-0023-7.
    1. Hamann C, Kirschner S, Gunther KP, Hofbauer LC. Bone, sweet bone--osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 2012;8(5):297–305.
    1. Chiang JI, Li TC, Li CI, Liu CS, Meng NH, Lin WY, et al. Visit-to-visit variation of fasting plasma glucose is a predictor of hip fracture in older persons with type 2 diabetes: the Taiwan diabetes study. Osteoporos Int. 2016;27(12):3587–3597. doi: 10.1007/s00198-016-3689-1.
    1. Ivers RQ, Cumming RG, Mitchell P, Peduto AJ. Blue Mountains eye S. diabetes and risk of fracture: the Blue Mountains eye study. Diabetes Care. 2001;24(7):1198–1203. doi: 10.2337/diacare.24.7.1198.
    1. Kim JH, Jung MH, Lee JM, Son HS, Cha BY, Chang SA. Diabetic peripheral neuropathy is highly associated with nontraumatic fractures in Korean patients with type 2 diabetes mellitus. Clin Endocrinol. 2012;77(1):51–55. doi: 10.1111/j.1365-2265.2011.04222.x.
    1. Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, et al. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int. 2018;29(12):2585–2596. doi: 10.1007/s00198-018-4650-2.
    1. Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the diagnosis and treatment of postmenopausal Osteoporosis-2020 update. Endocr Pract. 2020;26(Suppl 1):1–46. doi: 10.4158/GL-2020-0524SUPPL.
    1. Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological Management of Osteoporosis in postmenopausal women: an Endocrine Society guideline update. J Clin Endocrinol Metab. 2020;105(3).
    1. Cooper C, Emkey RD, McDonald RH, Hawker G, Bianchi G, Wilson K, et al. Efficacy and safety of oral weekly ibandronate in the treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab. 2003;88(10):4609–4615. doi: 10.1210/jc.2003-022029.
    1. Fernández-Real JM, Izquierdo M, Ortega F, Gorostiaga E, Gómez-Ambrosi J, Moreno-Navarrete JM, et al. The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab. 2009;94(1):237–245. doi: 10.1210/jc.2008-0270.
    1. Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP, et al. Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol. 2010;163(2):265–272. doi: 10.1530/EJE-10-0414.
    1. Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res. 2009;24(5):785–791. doi: 10.1359/jbmr.081234.
    1. Leu CT, Luegmayr E, Freedman LP, Rodan GA, Reszka AA. Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy. Bone. 2006;38(5):628–636. doi: 10.1016/j.bone.2005.07.023.
    1. Chesnut CH, 3rd, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, et al. Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis. J Bone Miner Res. 2004;19(8):1241–1249. doi: 10.1359/JBMR.040325.
    1. Miller PD, Recker RR, Reginster JY, Riis BJ, Czerwinski E, Masanauskaite D, et al. Efficacy of monthly oral ibandronate is sustained over 5 years: the MOBILE long-term extension study. Osteoporos Int. 2012;23(6):1747–1756. doi: 10.1007/s00198-011-1773-0.
    1. Schwartz AV. Efficacy of osteoporosis therapies in diabetic patients. Calcif Tissue Int. 2017;100(2):165–173. doi: 10.1007/s00223-016-0177-8.
    1. Anagnostis P, Paschou SA, Gkekas NN, Artzouchaltzi AM, Christou K, Stogiannou D, et al. Efficacy of anti-osteoporotic medications in patients with type 1 and 2 diabetes mellitus: a systematic review. Endocrine. 2018;60(3):373–383. doi: 10.1007/s12020-018-1548-x.
    1. Fan B, Lu Y, Genant H, Fuerst T, Shepherd J. Does standardized BMD still remove differences between Hologic and GE-lunar state-of-the-art DXA systems? Osteoporos Int. 2010;21(7):1227–1236. doi: 10.1007/s00198-009-1062-3.
    1. Lee YH, Song GG. Efficacy and safety of monthly 150 mg oral ibandronate in women with postmenopausal osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Korean J Intern Med. 2011;26(3):340–347. doi: 10.3904/kjim.2011.26.3.340.
    1. Harris ST, Reginster JY, Harley C, Blumentals WA, Poston SA, Barr CE, et al. Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: the eValuation of IBandronate efficacy (VIBE) database fracture study. Bone. 2009;44(5):758–765. doi: 10.1016/j.bone.2009.01.002.
    1. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int. 2007;18(4):427–444. doi: 10.1007/s00198-006-0253-4.
    1. de L, II, van der Klift M, de Laet CE, van Daele PL, Hofman A, Pols HA. Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam study. Osteoporos Int. 2005;16(12):1713–1720. doi: 10.1007/s00198-005-1909-1.
    1. Leslie WD, Aubry-Rozier B, Lamy O, Hans D. Manitoba bone density P. TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab. 2013;98(2):602–609. doi: 10.1210/jc.2012-3118.
    1. Kim JH, Choi HJ, Ku EJ, Kim KM, Kim SW, Cho NH, et al. Trabecular bone score as an indicator for skeletal deterioration in diabetes. J Clin Endocrinol Metab. 2015;100(2):475–482. doi: 10.1210/jc.2014-2047.
    1. Senn C, Gunther B, Popp AW, Perrelet R, Hans D, Lippuner K. Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study. Osteoporos Int. 2014;25(7):1945–1951. doi: 10.1007/s00198-014-2703-8.
    1. Di Gregorio S, Del Rio L, Rodriguez-Tolra J, Bonel E, García M, Winzenrieth R. Comparison between different bone treatments on areal bone mineral density (aBMD) and bone microarchitectural texture as assessed by the trabecular bone score (TBS) Bone. 2015;75:138–143. doi: 10.1016/j.bone.2014.12.062.
    1. Bandirali M, Di Leo G, Messina C, Pastor Lopez MJ, Mai A, Ulivieri FM, et al. Reproducibility of trabecular bone score with different scan modes using dual-energy X-ray absorptiometry: a phantom study. Skelet Radiol. 2015;44(4):573–576. doi: 10.1007/s00256-014-1980-9.
    1. Lewiecki EM, Keaveny TM, Kopperdahl DL, Genant HK, Engelke K, Fuerst T, et al. Once-monthly oral ibandronate improves biomechanical determinants of bone strength in women with postmenopausal osteoporosis. J Clin Endocrinol Metab. 2009;94(1):171–180. doi: 10.1210/jc.2008-1807.
    1. Eekman DA, Bultink IE, Heijboer AC, Dijkmans BA, Lems WF. Bone turnover is adequately suppressed in osteoporotic patients treated with bisphosphonates in daily practice. BMC Musculoskelet Disord. 2011;12:167. doi: 10.1186/1471-2474-12-167.
    1. Hygum K, Starup-Linde J, Harslof T, Vestergaard P, Langdahl BL. MECHANISMS IN ENDOCRINOLOGY: diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis. Eur J Endocrinol. 2017;176(3):R137–RR57. doi: 10.1530/EJE-16-0652.
    1. Purnamasari D, Puspitasari MD, Setiyohadi B, Nugroho P, Isbagio H. Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study. BMC Endocr Disord. 2017;17(1):72. doi: 10.1186/s12902-017-0224-0.
    1. Peron EP, Ogbonna KC, Donohoe KL. Antidiabetic medications and polypharmacy. Clin Geriatr Med 2015;31(1):17–27, vii.
    1. Schwartz AV, Schafer AL, Grey A, Vittinghoff E, Palermo L, Lui LY, et al. Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Miner Res. 2013;28(6):1348–1354. doi: 10.1002/jbmr.1865.
    1. Hong SH, Koo JW, Hwang JK, Hwang YC, Jeong IK, Ahn KJ, et al. Changes in serum osteocalcin are not associated with changes in glucose or insulin for osteoporotic patients treated with bisphosphonate. J Bone Metab. 2013;20(1):37–41. doi: 10.11005/jbm.2013.20.1.37.
    1. Karimi Fard M, Aminorroaya A, Kachuei A, Salamat MR, Hadi Alijanvand M, Aminorroaya Yamini S, et al. Alendronate improves fasting plasma glucose and insulin sensitivity, and decreases insulin resistance in prediabetic osteopenic postmenopausal women: A randomized triple-blind clinical trial. J Diabetes Investig. 2019;10(3):731–737. doi: 10.1111/jdi.12944.
    1. Viggers R, Al-Mashhadi Z, Starup-Linde J, Vestergaard P. Alendronate use and risk of type 2 diabetes: A Nationwide Danish nested case-control study. Front Endocrinol (Lausanne) 2021;12:771426. doi: 10.3389/fendo.2021.771426.
    1. Miller PD, McClung MR, Macovei L, Stakkestad JA, Luckey M, Bonvoisin B, et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study. J Bone Miner Res. 2005;20(8):1315–1322. doi: 10.1359/JBMR.050313.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera