Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis

Rizzoli, R.<sup>1</sup>; Chapurlat, R. D.<sup>2</sup>; Laroche, J.-M.<sup>3</sup>; Krieg, M. A.<sup>4</sup>; Thomas, T.<sup>5</sup>; Frieling, I.<sup>6</sup>; Boutroy, S.<sup>2</sup>; Laib, A.<sup>7</sup>; Bock, O.<sup>8</sup>; Felsenberg, D.<sup>8</sup>

Affiliations

¹Division of Bone Diseases, Department of Medical Specialties, Geneva University Hospitals and Faculty of Medicine, 1211 Geneva 14, Switzerland

²INSERM U831, Université de Lyon, Edouard Herriot Hospital, Lyon, France

³Rangueil Hospital, Toulouse, France

⁴Department of Musculoskeletal Medicine, CHUV, Lausanne, Switzerland

⁵INSERM U890, University Hospital, Saint-Etienne, France

⁶Osteoporosezentrum, Hamburg, Germany

⁷SCANCO Medical AG, Bruettisellen, Switzerland

⁸Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Centre of Muscle and Bone Research, Free University and Humboldt University, Berlin, Germany

Abstract and keywords

Summary: Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2 years, in postmenopausal osteoporotic women.

Introduction: Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk.

Methods: Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2 g/day) or alendronate (70 mg/week) for 2 years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers.

Results: In the intention-to-treat population (n = 83, age: 64 ± 8 years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2 years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated.

Conclusions: Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another method.

Keywords: Alendronate; Finite elements analysis; HR-pQCT; Microstructure; Osteoporosis; Strontium ranelate

Links

DOI: 10.1007/s00198-011-1758-z

PubMed: 21909729

WoS: 000298645700029

History

Received: 2011-05-13

Accepted: 2011-07-11

Online: 2011-09-10

Cited Works (28)

Year	Entry
2001	Homminga J, Huiskes R, Van Rietbergen B, Rüegsegger P, Weinans H. Introduction and evaluation of a gray-value voxel conversion technique. J Biomech. April 2001;34(4):513-517.
2000	Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. November 2000;27(5):687-694.
2008	MacNeil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. June 2008;42(6):1203-1213.
2010	Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S. A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res. December 2010;25(12):2558-2571.
2002	Pistoia W, van Rietbergen B, Lochmüller E-M, Lill CA, Eckstein F, Rüegsegger P. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. June 2002;30(6):842-848.
2010	Burghardt AJ, Kazakia GJ, Ramachandran S, Link TM, Majumdar S. Age- and gender-related differences in the geometric properties and biomechanical significance of intracortical porosity in the distal radius and tibia. J Bone Miner Res. May 2010;25(5):983-993.
2010	Seeman E, Delmas PD, Hanley DA, Sellmeyer D, Cheung AM, Shane E, Kearns A, Thomas T, Boyd SK, Boutroy S, Bogado C, Majumdar S, Fan M, Libanati C, Zanchetta J. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res. August 2010;25(8):1886-1894.
2003	Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF. Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res. November 2003;18(11):1932-1941.
1997	Laib A, Hildebrand T, Häuselmann HJ, Rüegsegger P. Ridge number density: a new parameter for in vivo bone structure analysis. Bone. December 1997;21(6):541-546.
2005	Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. December 2005;90(12):6508-6515.
1997	Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ. Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. September 15, 1997;100(6):1475-1480.
2011	Boyd SK, Szabo E, Ammann P. Increased bone strength is associated with improved bone microarchitecture in intact female rats treated with strontium ranelate: a finite element analysis study. Bone. May 2011;48(5):1109-1116.
2007	MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. December 2007;29(10):1096-1105.
2001	Dempster DW, Cosman F, Kurland ES, Zhou H, Nieves J, Woelfert L, Shane E, Plavetić K, Müller R, Bilezikian J, Lindsay R. Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study. J Bone Miner Res. October 2001;16(10):1846-1853.
2010	Nishiyama KK, Macdonald HM, Buie HR, Hanley DA, Boyd SK. Postmenopausal women with osteopenia have higher cortical porosity and thinner cortices at the distal radius and tibia than women with normal aBMD: an in vivo HR-pQCT study. J Bone Miner Res. April 2010;25(4):882-890.
2011	Macdonald HM, Nishiyama KK, Hanley DA, Boyd SK. Changes in trabecular and cortical bone microarchitecture at peripheral sites associated with 18 months of teriparatide therapy in postmenopausal women with osteoporosis. Osteoporos Int. January 2011;22(1):357-362.
1983	Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis: implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. October 1983;72(4):1396-1409.
1999	Turner CH, Rho J, Takano Y, Tsui TY, Pharr GM. The elastic properties of trabecular and cortical bone tissues are similar: results from two microscopic measurement techniques. J Biomech. April 1999;32(4):437-441.
1993	Turner CH, Burr DB. Basic biomechanical measurements of bone: a tutorial. Bone. 1993;14(4):595-608.
2007	MacNeil JA, Boyd SK. Load distribution and the predictive power of morphological indices in the distal radius and tibia by high resolution peripheral quantitative computed tomography. Bone. July 2007;41(1):129-137.
2010	Vilayphiou N, Boutroy S, Sornay-rendu E, Van rietbergen B, Munoz F, Delmas PD, Chapurlat R. Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in postmenopausal women. Bone. April 2010;46(4):1030-1037.
2010	Zebaze RMD, Ghasem-Zadeh A, Bohte A, Iuliano-Burns S, Mirams M, Price RI, Mackie EJ, Seeman E. Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study. Lancet. May 15, 2010;375(9727):1729-1736.
1996	Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet. December 7, 1996;348(9041):1535-1541.
2007	Sornay‐Rendu E, Boutroy S, Munoz F, Delmas PD. Alterations of cortical and trabecular architecture are associated with fractures in postmenopausal women, partially independent of decreased BMD measured by DXA: the OFELY study. J Bone Miner Res. March 2007;22(3):425-433.
1995	van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech. January 1995;28(1):69-81.
2006	Seeman E, Delmas PD. Bone quality: the material and structural basis of bone strength and fragility. NEJM. May 25, 2006;354(21):2250-2261.
2009	Sornay-Rendu E, Cabrera-Bravo J-L, Boutroy S, Munoz F, Delmas PD. Severity of vertebral fractures is associated with alterations of cortical architecture in postmenopausal women. J Bone Miner Res. April 2009;24(4):737-743.
1999	Laib A, Rüegsegger P. Calibration of trabecular bone structure measurements of in vivo three-dimensional peripheral quantitative computed tomography with 28-μm-resolution microcomputed tomography. Bone. January 1999;24(1):35-39.

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Year	Entry
2014	Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat J-B, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. June 2014;63:147-157.
2013	Cheung AM, Adachi JD, Hanley DA, Kendler DL, Davison KS, Josse R, Brown JP, Ste-Marie L-G, Kremer R, Erlandson MC, Dian L, Burghardt AJ, Boyd SK. High-resolution peripheral quantitative computed tomography for the assessment of bone strength and structure: a review by the Canadian Bone Strength Working Group. Curr Osteoporos Rep. June 2013;11(2):136-146.
2013	Nishiyama KK, Shane E. Clinical imaging of bone microarchitecture with HR-pQCT. Curr Osteoporos Rep. June 2013;11(2):147-155.
2015	van Rietbergen B, Ito K. A survey of micro-finite element analysis for clinical assessment of bone strength: the first decade. J Biomech. March 18, 2015;48(5):832-841.
2013	Hansen S, Hauge EM, Jensen J-EB, Brixen K. Differing effects of PTH 1–34, PTH 1–84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT. J Bone Miner Res. April 2013;28(4):736-745.
2017	Tsai JN, Nishiyama KK, Lin D, Yuan A, Lee H, Bouxsein ML, Leder BZ. Effects of denosumab and teriparatide transitions on bone microarchitecture and estimated strength: the DATA-Switch HR-pQCT study. J Bone Miner Res. October 2017;32(10):2001-2009.
2020	Kemp TD, de Bakker CMJ, Gabel L, Hanley DA, Billington EO, Burt LA, Boyd SK. Longitudinal bone microarchitectural changes are best detected using image registration. Osteoporos Int. October 2020;31(10):1995-2005.
2015	Zhou B. Bone Quality Assessment Using High Resolution Peripheral Quantitative Computed Tomography (HR-PQCT) [PhD thesis]. Columbia University; 2015.
2012	Dall'Ara E. QCT Based Finite Element Models of the Human Vertebra and Femur: Validation With Experiments and Comparison With Bone Densitometry [PhD thesis]. Vienna University of Technology; October 2012.
2013	Wu Y. Compositional and Material Properties of Rat Bone After Drug Treatment [PhD thesis]. Edmonton, AB: University of Alberta; 2013.
2021	Kemp TD. An Inverse Interface Evolution Problem to Identify Participant-Specific Bone Microarchitecture Adaptation [Master's thesis]. Calgary, AB: University of Calgary; May 2021.