Effect of denosumab on trabecular bone score in postmenopausal women with osteoporosis
Trabecular bone score (TBS) assesses bone quality in the lumbar spine using dual-energy X-ray absorptiometry (DXA) scans. In postmenopausal women with osteoporosis, denosumab significantly improved TBS independently of bone mineral density (BMD). This practical technique may have a role in managing patients with osteoporosis.
TBS, a gray-level texture index determined from lumbar spine DXA scans, correlates with bone microarchitecture and enhances assessment of vertebral fracture risk independently of BMD. In the FREEDOM study, denosumab increased BMD and reduced new vertebral fractures in postmenopausal women with osteoporosis. This retrospective analysis explored the effect of denosumab on TBS and the association between TBS and BMD in FREEDOM.
Postmenopausal women with lumbar spine or total hip BMD T-score <−2.5 and −4.0 or higher at both sites received placebo or denosumab 60 mg subcutaneously every 6 months. TBS indices were determined from DXA scans at baseline and months 12, 24, and 36 in a subset of 285 women (128 placebo, 157 denosumab) who had TBS values at baseline and ≥1 postbaseline visit.
Baseline characteristics were comparable between treatment groups; mean (SD) lumbar spine BMD T-score was −2.79 (0.64), and mean (standard deviation [SD]) TBS was 1.200 (0.101) overall. In the placebo group, BMD and TBS increased by ≤0.2% or decreased from baseline at each visit. In the denosumab group, progressive increases from baseline at 12, 24, and 36 months were observed for BMD (5.7, 7.8, and 9.8%) and TBS (1.4, 1.9, and 2.4%). Percentage changes in TBS were statistically significant compared with baseline (p < 0.001) and placebo (p ≤ 0.014). TBS was largely unrelated to BMD, regardless of treatment, either at baseline or for annual changes from baseline (all r2 ≤ 0.06).
In postmenopausal women with osteoporosis, denosumab significantly improved TBS independently of BMD.
KeywordsDenosumab Postmenopausal women Trabecular bone score
- 1.(1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser 843:1–129Google Scholar
- 2.Johnell O, Kanis JA, Oden A, Johansson H, De Laet C, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton LJ 3rd, O’Neill T, Pols H, Reeve J, Silman A, Tenenhouse A (2005) Predictive value of BMD for hip and other fractures. J Bone Miner Res 20:1185–1194CrossRefPubMedGoogle Scholar
- 6.Pothuaud L, Barthe N, Krieg MA, Mehsen N, Carceller P, Hans D (2009) Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study. J Clin Densitom 12:170–176CrossRefPubMedGoogle Scholar
- 7.Winzenrieth R, Michelet F, Hans D (2013) Three-dimensional (3D) microarchitecture correlations with 2D projection image gray-level variations assessed by trabecular bone score using high-resolution computed tomographic acquisitions: effects of resolution and noise. J Clin Densitom 16:287–296CrossRefPubMedGoogle Scholar
- 8.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
- 11.Nassar K, Paternotte S, Kolta S, Fechtenbaum J, Roux C, Briot K (2014) Added value of trabecular bone score over bone mineral density for identification of vertebral fractures in patients with areal bone mineral density in the non-osteoporotic range. Osteoporos Int 25:243–249CrossRefPubMedGoogle Scholar
- 14.Rabier B, Héraud A, Grand-Lenoir C, Winzenrieth R, Hans D (2010) A multicentre, retrospective case-control study assessing the role of trabecular bone score (TBS) in menopausal Caucasian women with low areal bone mineral density (BMDa): analysing the odds of vertebral fracture. Bone 46:176–181CrossRefPubMedGoogle Scholar
- 20.McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H, Barkmann R, Boutroy S, Brown J, Chapurlat R, Elders PJ, Fujita Y, Glüer 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, Mellström 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
- 22.Harvey NC, Glüer CC, Binkley N, McCloskey EV, Brandi ML, Cooper C, Kendler D, Lamy O, Laslop A, Camargos BM, Reginster JY, Rizzoli R, Kanis JA (2015) Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice. Bone 78:216–224CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Silva BC, Broy SB, Boutroy S, Schousboe JT, Shepherd JA, Leslie WD (2015) Fracture risk prediction by non-BMD DXA measures: the 2015 ISCD Official Positions Part 2: trabecular bone score. J Clin Densitom 18:309–330Google Scholar
- 26.Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176CrossRefPubMedGoogle Scholar
- 27.Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95:3597–3602CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765CrossRefPubMedGoogle Scholar
- 31.Bolognese MA, Teglbjærg CS, Zanchetta JR, Lippuner K, McClung MR, Brandi ML, Høiseth A, Lakatos P, Moffett AH, Lorenc RS, Wang A, Libanati C (2013) Denosumab significantly increases DXA BMD at both trabecular and cortical sites: results from the FREEDOM study. J Clin Densitom 16:147–153CrossRefPubMedGoogle Scholar
- 32.Reid IR, Miller PD, Brown JP, Kendler DL, Fahrleitner-Pammer A, Valter I, Maasalu K, Bolognese MA, Woodson G, Bone H, Ding B, Wagman RB, San Martin J, Ominsky MS, Dempster DW (2010) Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res 25:2256–2265CrossRefPubMedGoogle Scholar
- 33.Keaveny TM, McClung MR, Genant HK, Zanchetta JR, Kendler D, Brown JP, Goemaere S, Recknor C, Brandi ML, Eastell R, Kopperdahl DL, Engelke K, Fuerst T, Radcliffe HS, Libanati C (2014) Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. J Bone Miner Res 29:158–165CrossRefPubMedGoogle Scholar
- 34.Hans D, Krieg M, Lamy O, Felsenberg D (2012) Beneficial effects of strontium ranelate compared to alendronate on trabecular bone score in post menopausal osteoporotic women. A 2-year study (abstract). Osteoporos Int 23(Suppl 2):S266–S267Google Scholar
- 36.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
- 38.Senn C, Günther 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
- 39.Austin M, Yang YC, Vittinghoff E, Adami S, Boonen S, Bauer DC, Bianchi G, Bolognese MA, Christiansen C, Eastell R, Grauer A, Hawkins F, Kendler DL, Oliveri B, McClung MR, Reid IR, Siris ES, Zanchetta J, Zerbini CA, Libanati C, Cummings SR, FREEDOM Trial (2012) Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures. J Bone Miner Res 27:687–693CrossRefPubMedPubMedCentralGoogle Scholar