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Erschienen in: Osteoporosis International 2/2019

28.11.2018 | Original Article

Young’s modulus and hardness of human trabecular bone with bisphosphonate treatment durations up to 20 years

verfasst von: D. Pienkowski, C. L. Wood, H. H. Malluche

Erschienen in: Osteoporosis International | Ausgabe 2/2019

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Abstract

Summary

Bone modulus from patients with osteoporosis treated with bisphosphonates for 1 to 20 years was analyzed. Modulus increases during the first 6 years of treatment and remains unchanged thereafter.

Introduction

Bisphosphonates are widely used for treating osteoporosis, but the relationship between treatment duration and bone quality is unclear. Since material properties partially determine bone quality, the present study quantified the relationship between human bone modulus and hardness with bisphosphonate treatment duration.

Methods

Iliac crest bone samples from a consecutive case series of 86 osteoporotic Caucasian women continuously treated with oral bisphosphonates for 1.1–20 years were histologically evaluated to assess bone turnover and then tested using nanoindentation. Young’s modulus and hardness were measured and related to bisphosphonate treatment duration by statistical modeling.

Results

All bone samples had low bone turnover. Statistical models showed that with increasing bisphosphonate treatment duration, modulus and hardness increased, peaked, and plateaued. These models used quadratic terms to model modulus increases from 1 to 6 years of bisphosphonate treatment and linear terms to model modulus plateaus from 6 to 20 years of treatment. The treatment duration at which the quadratic–linear transition (join point) occurred also depended upon trabecular location. Hardness increased and peaked at 12.4 years of treatment; it remained constant for the next 7.6 years of treatment and was insensitive to trabecular location.

Conclusions

Bone modulus increases with bisphosphonate treatment durations up to 6 years, no additional modulus increases occurred after 6 years of treatment. Although hardness increased, peaked at 12.4 years and remained constant for the next 7.6 years of BP treatment, the clinical relevance of hardness remains unclear.
Literatur
2.
Zurück zum Zitat Schmidt GA, Horner KE, McDanel DL, Ross MB, Moores KG (2010) Risks and benefits of long-term bisphosphonate therapy. Am J Health Syst Pharm 67:994–1001CrossRefPubMed Schmidt GA, Horner KE, McDanel DL, Ross MB, Moores KG (2010) Risks and benefits of long-term bisphosphonate therapy. Am J Health Syst Pharm 67:994–1001CrossRefPubMed
3.
Zurück zum Zitat Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRefPubMedPubMedCentral Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–35CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526CrossRefPubMedPubMedCentral Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat (2016) The duration and safety of osteoporosis treatment. Abrahamsen B and Stuart Silverman S (eds). Springer International Publishing, pp. 17-36 (2016) The duration and safety of osteoporosis treatment. Abrahamsen B and Stuart Silverman S (eds). Springer International Publishing, pp. 17-36
6.
Zurück zum Zitat Hollick RJ, Reid DM (2011) Role of bisphosphonates in the management of postmenopausal osteoporosis: an update on recent safety anxieties. Menopause Int 17:66–72CrossRefPubMed Hollick RJ, Reid DM (2011) Role of bisphosphonates in the management of postmenopausal osteoporosis: an update on recent safety anxieties. Menopause Int 17:66–72CrossRefPubMed
7.
Zurück zum Zitat Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix A (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082CrossRefPubMed Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix A (1998) Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 280:2077–2082CrossRefPubMed
8.
Zurück zum Zitat Miller PD (2016) Underdiagnosis and undertreatment of osteoporosis: the battle to be won. J Clin Endocrinol Metab 101:852–859CrossRefPubMed Miller PD (2016) Underdiagnosis and undertreatment of osteoporosis: the battle to be won. J Clin Endocrinol Metab 101:852–859CrossRefPubMed
9.
Zurück zum Zitat Burr DB, Lane JE, Howe TS, Ng AC, Ebeling PR (2017) Response to PD Miller, Underdiagnosis and undertreatment of osteoporosis: the battle to be won. J Clin Endocrinol Metab 102:1088–1089PubMed Burr DB, Lane JE, Howe TS, Ng AC, Ebeling PR (2017) Response to PD Miller, Underdiagnosis and undertreatment of osteoporosis: the battle to be won. J Clin Endocrinol Metab 102:1088–1089PubMed
10.
Zurück zum Zitat Boskey AL, Spevak L, Weinstein RS (2009) Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int 20:793–800CrossRefPubMed Boskey AL, Spevak L, Weinstein RS (2009) Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int 20:793–800CrossRefPubMed
11.
Zurück zum Zitat Bala Y, Farlay D, Chapurlat RD, Boivin G (2011) Modifications of bone material properties in postmenopausal osteoporotic women long-term treated with alendronate. Eur J Endocrinol 165:647–655CrossRefPubMed Bala Y, Farlay D, Chapurlat RD, Boivin G (2011) Modifications of bone material properties in postmenopausal osteoporotic women long-term treated with alendronate. Eur J Endocrinol 165:647–655CrossRefPubMed
12.
Zurück zum Zitat Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL (2010) Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone 46:666–672CrossRefPubMed Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL (2010) Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone 46:666–672CrossRefPubMed
13.
Zurück zum Zitat Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D (2009) Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int 20:887–894CrossRefPubMed Tang SY, Allen MR, Phipps R, Burr DB, Vashishth D (2009) Changes in non-enzymatic glycation and its association with altered mechanical properties following 1-year treatment with risedronate or alendronate. Osteoporos Int 20:887–894CrossRefPubMed
14.
Zurück zum Zitat Day JS, Ding M, Bednarz P, van der Linden JC, Mashiba T, Hirano T, Johnston CC, Burr DB, Hvid I, Sumner DR, Weinans H (2004) Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties. J Orthop Res 22:465–471CrossRefPubMed Day JS, Ding M, Bednarz P, van der Linden JC, Mashiba T, Hirano T, Johnston CC, Burr DB, Hvid I, Sumner DR, Weinans H (2004) Bisphosphonate treatment affects trabecular bone apparent modulus through micro-architecture rather than matrix properties. J Orthop Res 22:465–471CrossRefPubMed
15.
Zurück zum Zitat Ward J, Wood CL, Pienkowski D, Malluche HH (2016) Stiffness and strength of bone in osteoporotic patients treated with varying durations of oral bisphosphonates. Osteoporos Int 27:2681–2688CrossRefPubMed Ward J, Wood CL, Pienkowski D, Malluche HH (2016) Stiffness and strength of bone in osteoporotic patients treated with varying durations of oral bisphosphonates. Osteoporos Int 27:2681–2688CrossRefPubMed
16.
Zurück zum Zitat Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15:613–620CrossRefPubMed Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15:613–620CrossRefPubMed
17.
Zurück zum Zitat Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, Chapurlat R, Chevalier J, Boivin G (2012) Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. J Bone Miner Res 27:825–834CrossRefPubMed Bala Y, Depalle B, Farlay D, Douillard T, Meille S, Follet H, Chapurlat R, Chevalier J, Boivin G (2012) Bone micromechanical properties are compromised during long-term alendronate therapy independently of mineralization. J Bone Miner Res 27:825–834CrossRefPubMed
18.
Zurück zum Zitat Mosekilde L, Viidik A, Mosekilde L (1985) Correlation between the compressive strength of iliac and vertebral trabecular bone in normal individuals. Bone 6:291–295CrossRefPubMed Mosekilde L, Viidik A, Mosekilde L (1985) Correlation between the compressive strength of iliac and vertebral trabecular bone in normal individuals. Bone 6:291–295CrossRefPubMed
19.
Zurück zum Zitat Britton JM, Davie MW (1990) Mechanical properties of bone from iliac crest and relationship to L5 vertebral bone. Bone 11:21–28CrossRefPubMed Britton JM, Davie MW (1990) Mechanical properties of bone from iliac crest and relationship to L5 vertebral bone. Bone 11:21–28CrossRefPubMed
20.
Zurück zum Zitat Monier-Faugere MC, Langub MC, Malluche HH (1997) Bone biopsies: a modern approach. In: Avioli LV, Krane SM (eds) Metabolic bone disease, 3rd edn. WB Saunders Co, pp 237–273 Monier-Faugere MC, Langub MC, Malluche HH (1997) Bone biopsies: a modern approach. In: Avioli LV, Krane SM (eds) Metabolic bone disease, 3rd edn. WB Saunders Co, pp 237–273
21.
Zurück zum Zitat Malluche HHMH, Monier-Faugere MC (2008) Bone biopsy in patients with osteoporosis. Curr Osteoporosis Rep 5:146–152CrossRef Malluche HHMH, Monier-Faugere MC (2008) Bone biopsy in patients with osteoporosis. Curr Osteoporosis Rep 5:146–152CrossRef
22.
Zurück zum Zitat Malluche HH and Monier-Faugere MC (1986) Atlas of mineralized bone histology. Karger, Basel, pp. 18–25. Malluche HH and Monier-Faugere MC (1986) Atlas of mineralized bone histology. Karger, Basel, pp. 18–25.
23.
Zurück zum Zitat Rho JY, Tsui TY, Pharr GM (1997) Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation. Biomaterials 18:1325–1330CrossRefPubMed Rho JY, Tsui TY, Pharr GM (1997) Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation. Biomaterials 18:1325–1330CrossRefPubMed
24.
Zurück zum Zitat Malluche HH, Porter DS, Monier-Faugere MC, Mawad H, Pienkowski D (2012) Differences in bone quality in low- and high-turnover renal osteodystrophy. J Am Soc Nephrol 23:525–532CrossRefPubMedPubMedCentral Malluche HH, Porter DS, Monier-Faugere MC, Mawad H, Pienkowski D (2012) Differences in bone quality in low- and high-turnover renal osteodystrophy. J Am Soc Nephrol 23:525–532CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Oliver WC, Pharr GM (2004) Measurement of hardness and elastic modulus by instrumented indentation: advances in understanding and refinements to methodology. J Mater Res 19:3–20CrossRef Oliver WC, Pharr GM (2004) Measurement of hardness and elastic modulus by instrumented indentation: advances in understanding and refinements to methodology. J Mater Res 19:3–20CrossRef
26.
Zurück zum Zitat Oliver WC, Pharr GM (1992) An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiment. J Mater Res 7:1564–1583CrossRef Oliver WC, Pharr GM (1992) An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiment. J Mater Res 7:1564–1583CrossRef
27.
Zurück zum Zitat Donnelly E, Meredith DS, Nguyen JT, Boskey AL (2012) Bone tissue composition varies across anatomic sites in the proximal femur and the iliac crest. J Orthop Res 30:700–706CrossRefPubMed Donnelly E, Meredith DS, Nguyen JT, Boskey AL (2012) Bone tissue composition varies across anatomic sites in the proximal femur and the iliac crest. J Orthop Res 30:700–706CrossRefPubMed
28.
Zurück zum Zitat Fan Z, Rho JY (2003) Effects of viscoelasticity and time-dependent plasticity on nanoindentation measurements of human cortical bone. J Biomed Mater Res A 67:208–214CrossRefPubMed Fan Z, Rho JY (2003) Effects of viscoelasticity and time-dependent plasticity on nanoindentation measurements of human cortical bone. J Biomed Mater Res A 67:208–214CrossRefPubMed
29.
Zurück zum Zitat Zoehrer R, Roschger P, Paschalis EP, Hofstaetter JG, Durchschlag E, Fratzl P, Phipps R, Klaushofer K (2006) Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women. J Bone Miner Res 21:1106–1112CrossRefPubMed Zoehrer R, Roschger P, Paschalis EP, Hofstaetter JG, Durchschlag E, Fratzl P, Phipps R, Klaushofer K (2006) Effects of 3- and 5-year treatment with risedronate on bone mineralization density distribution in triple biopsies of the iliac crest in postmenopausal women. J Bone Miner Res 21:1106–1112CrossRefPubMed
30.
Zurück zum Zitat Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191CrossRefPubMed Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191CrossRefPubMed
31.
Zurück zum Zitat Tjhia CK, Stover SM, Rao DS, Odvina CV, Fyhrie DP (2012) Relating micromechanical properties and mineral densities in severely suppressed bone turnover patients, osteoporotic patients, and normal subjects. Bone 51:114–122CrossRefPubMedPubMedCentral Tjhia CK, Stover SM, Rao DS, Odvina CV, Fyhrie DP (2012) Relating micromechanical properties and mineral densities in severely suppressed bone turnover patients, osteoporotic patients, and normal subjects. Bone 51:114–122CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Maruyama N, Shibata Y, Wurihan, Swain MV, Kataoka Y, Takiguchi Y, Yamada A, Maki K, Miyazaki T (2014) Strain-rate stiffening of cortical bone: observations and implications from nanoindentation experiments. Nanoscale 6:14863–14871CrossRefPubMed Maruyama N, Shibata Y, Wurihan, Swain MV, Kataoka Y, Takiguchi Y, Yamada A, Maki K, Miyazaki T (2014) Strain-rate stiffening of cortical bone: observations and implications from nanoindentation experiments. Nanoscale 6:14863–14871CrossRefPubMed
33.
Zurück zum Zitat Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR, Fracture Intervention T (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124CrossRefPubMed Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR, Fracture Intervention T (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124CrossRefPubMed
34.
Zurück zum Zitat Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ (1997) Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100:1475–1480CrossRefPubMedPubMedCentral Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ (1997) Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100:1475–1480CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Hoffler CE, Moore KE, Kozloff K, Zysset PK, Goldstein SA (2000) Age, gender, and bone lamellae elastic moduli. J Orthop Res 18:432–437CrossRefPubMed Hoffler CE, Moore KE, Kozloff K, Zysset PK, Goldstein SA (2000) Age, gender, and bone lamellae elastic moduli. J Orthop Res 18:432–437CrossRefPubMed
36.
Zurück zum Zitat Ding M, Dalstra M, Danielsen CC, Kabel J, Hvid I, Linde F (1997) Age variations in the properties of human tibial trabecular bone. J Bone Joint Surg (Br) 79:995–1002CrossRef Ding M, Dalstra M, Danielsen CC, Kabel J, Hvid I, Linde F (1997) Age variations in the properties of human tibial trabecular bone. J Bone Joint Surg (Br) 79:995–1002CrossRef
37.
Zurück zum Zitat Wang X, Allen MR, Burr DB, Lavernia EJ, Jeremic B, Fyhrie DP (2008) Identification of material parameters based on Mohr-Coulomb failure criterion for bisphosphonate treated canine vertebral cancellous bone. Bone 43:775–780CrossRefPubMedPubMedCentral Wang X, Allen MR, Burr DB, Lavernia EJ, Jeremic B, Fyhrie DP (2008) Identification of material parameters based on Mohr-Coulomb failure criterion for bisphosphonate treated canine vertebral cancellous bone. Bone 43:775–780CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Zysset PK, Guo XE, Hoffler CE, Moore KE, Goldstein SA (1999) Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur. J Biomech 32:1005–1012CrossRefPubMed Zysset PK, Guo XE, Hoffler CE, Moore KE, Goldstein SA (1999) Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur. J Biomech 32:1005–1012CrossRefPubMed
39.
Zurück zum Zitat Mittra E, Akella S, Qin YX (2006) The effects of embedding material, loading rate and magnitude, and penetration depth in nanoindentation of trabecular bone. J Biomed Mater Res A 79:86–93CrossRefPubMed Mittra E, Akella S, Qin YX (2006) The effects of embedding material, loading rate and magnitude, and penetration depth in nanoindentation of trabecular bone. J Biomed Mater Res A 79:86–93CrossRefPubMed
40.
Zurück zum Zitat Bushby AJ, Ferguson VL, Boyde A (2004) Nanoindentation of bone: comparison of specimens tested in liquid and embedded in polymethylmethacrylate. J Mater Res 19:249–259CrossRef Bushby AJ, Ferguson VL, Boyde A (2004) Nanoindentation of bone: comparison of specimens tested in liquid and embedded in polymethylmethacrylate. J Mater Res 19:249–259CrossRef
41.
Zurück zum Zitat Rho JY, Pharr GM (1999) Effects of drying on the mechanical properties of bovine femur measured by nanoindentation. J Mater Sci Mater Med 10:485–488CrossRefPubMed Rho JY, Pharr GM (1999) Effects of drying on the mechanical properties of bovine femur measured by nanoindentation. J Mater Sci Mater Med 10:485–488CrossRefPubMed
42.
Zurück zum Zitat Li ZC, Dai LY, Jiang LS, Qiu S (2012) Difference in subchondral cancellous bone between postmenopausal women with hip osteoarthritis and osteoporotic fracture: implication for fatigue microdamage, bone microarchitecture, and biomechanical properties. Arthritis Rheum 64:3955–3962CrossRefPubMed Li ZC, Dai LY, Jiang LS, Qiu S (2012) Difference in subchondral cancellous bone between postmenopausal women with hip osteoarthritis and osteoporotic fracture: implication for fatigue microdamage, bone microarchitecture, and biomechanical properties. Arthritis Rheum 64:3955–3962CrossRefPubMed
43.
Zurück zum Zitat Brody JE (2018) A perfect storm for broken bones. The New York Times, New York Brody JE (2018) A perfect storm for broken bones. The New York Times, New York
Metadaten
Titel
Young’s modulus and hardness of human trabecular bone with bisphosphonate treatment durations up to 20 years
verfasst von
D. Pienkowski
C. L. Wood
H. H. Malluche
Publikationsdatum
28.11.2018
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 2/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-018-4760-x

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