Effects of Teriparatide and Sequential Minodronate on Lumbar Spine Bone Mineral Density and Microarchitecture in Osteoporosis
The trabecular bone score (TBS) is a new surrogate for trabecular bone microarchitecture assessment, independent of bone mineral density (BMD), calculated from pixel gray-level variations in the lumbar spine (LS) dual-energy X-ray absorptiometry (DXA) image. Although Teriparatide (TPTD) increased LS-BMD as well as TBS in 2 years, the precise time-course of these parameters was not well known. The aim of this study was to determine the changes in LS-BMD and the TBS in osteoporotic patients treated with TPTD, followed by minodronate (MINO). Primary osteoporotic patients with a low LS-BMD (T-score < −2.5) and/or at least one vertebral fracture were treated with TPTD subcutaneously at 20 µg/day for 12–24 months, followed by MINO (orally at 50 mg/once monthly) for 12 months. LS-BMD and the TBS were measured at 0, 3, 6, 12, and 24 months after the initiation of TPTD treatment, and 12 months after the initiation of MINO. The increments of LS-BMD, significant at 6 months, increased until 12 months, whereas the increments of TBS, significant at 3 months (0.035 ± 0.011; p = 0.045 vs. the baseline), stabilized until 12 months. TPTD treatment, followed by 12 months of MINO, maintained both BMD and the TBS. Comparing the increments of the TBS to those of LS-BMD, our results indicate that TPTD treatment improved trabecular microarchitecture faster than mineralization. TPTD treatment, followed by MINO, can maintain both BMD and the TBS.
KeywordsOsteoporosis Teriparatide Minodronate Bone mineral density Trabecular bone score
DM contributed to the acquisition, analysis, and interpretation of the data. YI, ME, and MI contributed to the conception and design of the study. MO, NH, YN, SY, and KM contributed to the acquisition of the data. DM took responsibility for the integrity of the data analysis. All authors participated in drafting or revising the manuscript and approved the final version of the manuscript for submission.
MI received grant support and lecture fees from Eli Lilly Japan K.K. and Ono Pharmaceutical Co., LTD. YI and KM received lecture fees from Eli Lilly Japan K.K. and Ono Pharmaceutical Co., LTD.
Compliance with Ethical Standards
Conflicts of interest
Daichi Miyaoka, Masaya Ohara, Noriyuki Hayashi, Yuki Nagata, Shinsuke Yamada, and Masanori Emoto have no conflicts of interest.
Human and Animal Rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study, which received institutional ethics committee approval (Osaka City University Graduate School of Medicine, registration number 1775).
- 2.McCloskey EV, Oden A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, Elders PJ, Fujita Y, Gluer CC, Goltzman D, Iki M, Karlsson M, Kindmark A, Kotowicz M, Kurumatani N, Kwok T, Lamy O, Leung J, Lippuner K, Ljunggren O, Lorentzon M, Mellstrom D, Merlijn T, Oei L, Ohlsson C, Pasco JA, Rivadeneira F, Rosengren B, Sornay-Rendu E, Szulc P, Tamaki J, Kanis JA (2016) A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Miner Res 31:940–948CrossRefPubMedGoogle Scholar
- 3.Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA (2011) Correlations between trabecular bone score, measured using anteroposterior dual-energy X-ray absorptiometry acquisition, and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom 14:302–312CrossRefPubMedGoogle Scholar
- 5.Silva BC, Boutroy S, Zhang C, McMahon DJ, Zhou B, Wang J, Udesky J, Cremers S, Sarquis M, Guo XD, Hans D, Bilezikian JP (2013) Trabecular bone score (TBS)—a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 98:1963–1970CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Silva BC, Walker MD, Abraham A, Boutroy S, Zhang C, McMahon DJ, Liu G, Hans D, Bilezikian JP (2013) Trabecular bone score is associated with volumetric bone density and microarchitecture as assessed by central QCT and HRpQCT in Chinese American and White women. J Clin Densitom 16:554–561CrossRefPubMedGoogle Scholar
- 11.Iki M, Tamaki J, Kadowaki E, Sato Y, Dongmei N, Winzenrieth R, Kagamimori S, Kagawa Y, Yoneshima H (2014) Trabecular bone score (TBS) predicts vertebral fractures in Japanese women over 10 years independently of bone density and prevalent vertebral deformity: the Japanese Population-Based Osteoporosis (JPOS) cohort study. J Bone Miner Res 29:399–407CrossRefPubMedGoogle Scholar
- 12.Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441CrossRefPubMedGoogle Scholar
- 13.Senn C, Gunther B, Popp AW, Perrelet R, Hans D, Lippuner K (2014) 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 25:1945–1951CrossRefPubMedGoogle Scholar
- 17.Eastell R, Nickelsen T, Marin F, Barker C, Hadji P, Farrerons J, Audran M, Boonen S, Brixen K, Gomes JM, Obermayer-Pietsch B, Avramidis A, Sigurdsson G, Gluer CC (2009) Sequential treatment of severe postmenopausal osteoporosis after teriparatide: final results of the randomized, controlled European Study of Forsteo (EUROFORS). J Bone Miner Res 24:726–736CrossRefPubMedGoogle Scholar
- 20.Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) Structure-activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242PubMedGoogle Scholar
- 23.Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The study of osteoporotic fractures research group. J Bone Miner Res 11:984–996CrossRefPubMedGoogle Scholar
- 25.Gao P, Scheibel S, D’Amour P, John MR, Rao SD, Schmidt-Gayk H, Cantor TL (2001) Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1–84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 16:605–614CrossRefPubMedGoogle Scholar
- 29.Misof BM, Roschger P, Cosman F, Kurland ES, Tesch W, Messmer P, Dempster DW, Nieves J, Shane E, Fratzl P, Klaushofer K, Bilezikian J, Lindsay R (2003) Effects of intermittent parathyroid hormone administration on bone mineralization density in iliac crest biopsies from patients with osteoporosis: a paired study before and after treatment. J Clin Endocrinol Metab 88:1150–1156CrossRefPubMedGoogle Scholar
- 32.Saag KG, Agnusdei D, Hans D, Kohlmeier LA, Krohn KD, Leib ES, MacLaughlin EJ, Alam J, Simonelli C, Taylor KA, Marcus R (2016) Trabecular bone score in patients with chronic glucocorticoid therapy-induced osteoporosis treated with alendronate or teriparatide. Arthritis Rheumatol 68:2122–2128CrossRefPubMedGoogle Scholar
- 36.Saag KG, Zanchetta JR, Devogelaer JP, Adler RA, Eastell R, See K, Krege JH, Krohn K, Warner MR (2009) Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: thirty-six-month results of a randomized, double-blind, controlled trial. Arthritis Rheum 60:3346–3355CrossRefPubMedGoogle Scholar
- 39.Popp AW, Guler S, Lamy O, Senn C, Buffat H, Perrelet R, Hans D, Lippuner K (2013) Effects of zoledronate versus placebo on spine bone mineral density and microarchitecture assessed by the trabecular bone score in postmenopausal women with osteoporosis: a three-year study. J Bone Miner Res 28:449–454CrossRefPubMedGoogle Scholar