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Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces
Abstracts Sanofi Aventis, Warner Chilcott, Wyeth, E. Franek Consulting fees from Amgen, Speaker Fees from Amgen, Novartis, Roche, Servier, E. Lewiecki Grant/Research Support from Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott, Genentech, Speakers Bureau with Amgen, Eli Lilly, Novartis, Merck, Genentech, C. Mautalen: none declared, S. Ragi Eis Grant/Research Support from Amgen, G. Nicholson Grant/Research Support from Amgen, C. Muschitz Consulting fees from Amgen, R. Nuti Consulting fees from Amgen, Eli Lilly, Servier, A. Wang Shareholder of Amgen, Employee of Amgen, C. Libanati Shareholder of Amgen, Employee of Amgen. doi:10.1016/j.bone.2012.02.147
OPC08 Relationship between change in total hip BMD in response to zoledronic acid 5 mg and pre-treatment change in total hip BMD: The HORIZON-PFT Extension study R. Eastella,⁎, L. Palermob, S. Boonenc, F. Cosmand, I. Reide, S. Cummingsf, D. Blackb a University of Sheffield, Sheffield, UK b University of California, San Francisco, San Francisco, USA c Center for Metabolic Bone Disease & Division of Geriatric Medicine, Leuven, Belgium d Helen Hayes Hospital, West Haverstraw, USA e University of Auckland, Auckland, New Zealand f San Francisco Coordinating Center, San Francisco, USA Abstract: Several studies have shown the high bone turnover is associated with 1) greater rates of bone loss and 2) greater BMD response to anti-resorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss prior to therapy are associated with greater BMD response to anti-resorptive therapy. In the HORIZON-PFT Extension study, one group of women who were randomized to receive placebo for 3 years (years 1, 2 and 3), were then all treated with Zoledronic Acid 5 mg annually for up to three injections (years 4, 5 and 6, P3Z3 Study) (n = 1223). We measured total hip BMD at baseline, 1, 2 and 3 years on placebo and at 4.5 and 6 years on zoledronic acid. BMD was measured by DXA and total PINP by automated immunoassay analyser. The PINP was measured at 3, 4.5 and 6 years, but results were excluded if patients had a fracture in the past year (PINP increases for up to a year following a fracture). Also, by design not all subjects were followed for as long as 6 years, so this analysis will focus on the results at 4.5 years. The change in total hip BMD in years 0–3 was related to the change in total hip BMD on zoledronic acid at 4.5 years (r = − 0.39, P b 0.0001). Thus, those with greater loss during years 0–3 had greater gain during years 3-4.5. In order to test whether this last result was robust, we repeated the analysis with hip BMD at 6 years (r = − 0.24, P b 0.0001) and we repeated the analysis with change in hip BMD at 2 years (r = − 0.09, P b 0.01). The change in total hip BMD in years 0–3 on placebo was related to the serum PINP at the end of the 3-year period (r = − 0.24, P b 0.0001). The change in total hip BMD on zoledronic acid from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r = 0.26, P b 0.0001).We conclude that BMD response to zoledronic acid is greater in postmenopausal women who had larger loss prior to treatment. The likely mechanism for this association is that higher bone turnover is associated with both greater BMD response to zoledronic acid and greater bone loss on placebo. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: R. Eastell Grant/Research Support from Warner Chilcott, Amgen, Eli Lilly, AstraZeneca, Consulting fees from AstraZeneca, Amgen, GlaxoSmithKline, Medtronics, Nastech, Nestle, Fonterra Brands, Novartis, Ono Pharma, Eli Lilly, Sanofi Aventis, Tethys, Unilever, L. Palermo: None Declared, S. Boonen Grant/Research Support from Amgen, Eli Lilly, Novartis, Pfizer, and Roche–GlaxoSmithKline, Consulting fees from Eli Lilly, Merck, Novartis, and Servier; Lecture Fees from Amgen, Eli Lilly, Merck, Novartis, and Servier, F. Cosman Grant/Research Support from Eli Lilly, Novartis, Consulting fees from Eli Lilly, Novartis, Merck, Amgen, Lecture Fees from Eli Lilly, Novartis, Amgen, I. Reid Grant/ Research Support from Amgen, Novartis, Procter & Gamble and Merck, Consulting fees from Merck, Amgen, Novartis, Lecture Fees from Merck, Amgen, Novartis, S. Cummings Grant/Research Support from Amgen, Consulting fees from Amgen, Eli Lilly, Merck, Lecture Fees from Eli Lilly, D. Black Grant/Research Support from Novartis, Merck, Roche and Amgen, Consulting fees from Eli Lilly, Amgen, Zosano, Radius, Nycomed. doi:10.1016/j.bone.2012.02.148
OPC09 Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces B. Hofstettera, S. Gamsjaegera,⁎, R.J. Phippsb, R.R. Reckerc, F.H. Ebetinod, K. Klaushofera, E.P. Paschalisa
S55
a
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Heinrich Collin Str. 30, A-1140, Vienna, Austria b University School of Pharmacy Husson, Bangor, USA c Osteoporosis Research Center, Creighton University, Omaha, USA d Warner Chilcott, Dundalk, Ireland
Abstract: In the present work we examined the effect of alendronate (ALN) and risedronate (RIS) treatment on bone material properties by Raman and Fourier Transform Infrared Imaging (FTIR) microspectroscopic analysis at actively bone forming trabecular surfaces. At 8 study sites, women were identified who had postmenopausal osteoporosis (PMO), were at least 5 year postmenopause and had been on long-term therapy (either 3–5 or N 5 years) with daily or weekly ALN or RIS. Following standard tetracycline labeling, biopsies were collected from 102 women (33 were treated with ALN for 3–5 years (ALN-3), 35 with ALN for N5 years (ALN-5), 26 with RIS for 3–5 years (RIS-3) and 8 with RIS for N 5 years (RIS-5)) and analyzed at anatomical areas of similar tissue age in bone forming areas (determined from the fluorescent labels). The parameters measured were mineral to matrix ratio (corresponding to ash weight), relative proteoglycan content (regulating mineralization initiation), mineral maturity (indicative of the mineral crystallite chemistry and stoichiometry, and having a direct bearing on crystallite shape and size), and the ratio of two of the major enzymatic collagen cross-links (pyridinoline/divalent). No significant differences in mineral/matrix ratio amongst the 4 groups were evident. Relative proteoglycan content was significantly lower in the patients receiving RIS long-term (RIS-5) compared to patients receiving long term ALN therapy (ALN-5). Similarly, this was significantly lower in the long-term RIS users compared to the short-term users (RIS-3 vs RIS-5). Mineral maturity/crystallinity as determined from Raman analysis was significantly lower in the RIS-3 and RIS-5 groups compared to the ALN-3 and ALN-5 groups, respectively. The pyr/divalent collagen cross-link ratio was significantly lower in RIS compared to ALN at both 3–5 and 5 years; additionally, the RIS-5 group had significantly lower values compared to the RIS-3 group. The results of the present study indicate that ALNand RIS exert differential effects on the intrinsic bone material properties at actively bone forming trabecular surfaces. This suggests that the two drugs achieve their antifracture efficacy via different mechanisms or influence the same mechanisms differently (e.g. bone affinity and enzyme inhibition). Additionally, these results emphasize the need to understand quantitative and qualitative effects on bone formation when evaluating drug performance. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: B. Hofstetter: None Declared, S. Gamsjaeger: none declared, R. Phipps Employee of Alliance for Better Bone Health, R. Recker: none declared, F. Ebetino Employee of Warner Chilcott, K. Klaushofer: none declared, E. Paschalis: none declared. doi:10.1016/j.bone.2012.02.149
OPC10 High physical capacity in young adulthood reduces the risk of fracture later in life P. Nordströma,⁎, H. Sievänenb, Y. Gustafsona, N. Pedersenc, A. Nordströmd a Geriatric Medicine, Umeå, Sweden b Health Promotion Research, Tampere, Finland c Karolinska Institute, Stockholm, Sweden d Rehabilitation Medicine, Umeå, Sweden Abstract: Context: Despite the impact of fractures on patients' quality of life and the healthcare burden, little is known about the influence of physical fitness in young adulthood on fracture risk later in life. Objective We investigated whether high aerobic fitness and muscle strength in young adulthood reduced the risk of low-energy fracture later in life in men. Design, setting, and participants: During national conscription tests conducted in Sweden in 1969–1978, the aerobic fitness and isometric muscle strength of 435,445 men (mean age, 18.5 years) were evaluated. Main outcome measure: Data on men who sustained low-energy fractures after the age of 40 years were collected from national registers. Results: During a median follow-up period of 35 years (range, 11–41 years), 8030 subjects sustained at least one low-energy fracture. After adjusting for potential confounders, the risk of low-energy fracture was 1.8 times higher (95% confidence interval, 1.6–2.1) and that of hip fracture was 2.7 times higher (95% confidence interval, 1.6–4.7) among men in the lowest decile of aerobic fitness than among those in the highest decile. The risk of low-energy fracture was also 1.4–1.5 times higher among men in the lowest deciles of knee extension strength, grip strength, and elbow flexion strength (p b 0.001 for all), compared with those in the highest deciles. Conclusion: The results of the present study show that low aerobic fitness and muscle strength in young adulthood were associated with an elevated risk of low-energy fracture more than 30 years later in men.
OPC08 Relationship between change in total hip BMD in response to zoledronic acid 5 mg and pre-treatment change in total hip BMD: The HORIZON-PFT Extension study R. Eastella,⁎, L. Palermob, S. Boonenc, F. Cosmand, I. Reide, S. Cummingsf, D. Blackb a University of Sheffield, Sheffield, UK b University of California, San Francisco, San Francisco, USA c Center for Metabolic Bone Disease & Division of Geriatric Medicine, Leuven, Belgium d Helen Hayes Hospital, West Haverstraw, USA e University of Auckland, Auckland, New Zealand f San Francisco Coordinating Center, San Francisco, USA Abstract: Several studies have shown the high bone turnover is associated with 1) greater rates of bone loss and 2) greater BMD response to anti-resorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss prior to therapy are associated with greater BMD response to anti-resorptive therapy. In the HORIZON-PFT Extension study, one group of women who were randomized to receive placebo for 3 years (years 1, 2 and 3), were then all treated with Zoledronic Acid 5 mg annually for up to three injections (years 4, 5 and 6, P3Z3 Study) (n = 1223). We measured total hip BMD at baseline, 1, 2 and 3 years on placebo and at 4.5 and 6 years on zoledronic acid. BMD was measured by DXA and total PINP by automated immunoassay analyser. The PINP was measured at 3, 4.5 and 6 years, but results were excluded if patients had a fracture in the past year (PINP increases for up to a year following a fracture). Also, by design not all subjects were followed for as long as 6 years, so this analysis will focus on the results at 4.5 years. The change in total hip BMD in years 0–3 was related to the change in total hip BMD on zoledronic acid at 4.5 years (r = − 0.39, P b 0.0001). Thus, those with greater loss during years 0–3 had greater gain during years 3-4.5. In order to test whether this last result was robust, we repeated the analysis with hip BMD at 6 years (r = − 0.24, P b 0.0001) and we repeated the analysis with change in hip BMD at 2 years (r = − 0.09, P b 0.01). The change in total hip BMD in years 0–3 on placebo was related to the serum PINP at the end of the 3-year period (r = − 0.24, P b 0.0001). The change in total hip BMD on zoledronic acid from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r = 0.26, P b 0.0001).We conclude that BMD response to zoledronic acid is greater in postmenopausal women who had larger loss prior to treatment. The likely mechanism for this association is that higher bone turnover is associated with both greater BMD response to zoledronic acid and greater bone loss on placebo. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: R. Eastell Grant/Research Support from Warner Chilcott, Amgen, Eli Lilly, AstraZeneca, Consulting fees from AstraZeneca, Amgen, GlaxoSmithKline, Medtronics, Nastech, Nestle, Fonterra Brands, Novartis, Ono Pharma, Eli Lilly, Sanofi Aventis, Tethys, Unilever, L. Palermo: None Declared, S. Boonen Grant/Research Support from Amgen, Eli Lilly, Novartis, Pfizer, and Roche–GlaxoSmithKline, Consulting fees from Eli Lilly, Merck, Novartis, and Servier; Lecture Fees from Amgen, Eli Lilly, Merck, Novartis, and Servier, F. Cosman Grant/Research Support from Eli Lilly, Novartis, Consulting fees from Eli Lilly, Novartis, Merck, Amgen, Lecture Fees from Eli Lilly, Novartis, Amgen, I. Reid Grant/ Research Support from Amgen, Novartis, Procter & Gamble and Merck, Consulting fees from Merck, Amgen, Novartis, Lecture Fees from Merck, Amgen, Novartis, S. Cummings Grant/Research Support from Amgen, Consulting fees from Amgen, Eli Lilly, Merck, Lecture Fees from Eli Lilly, D. Black Grant/Research Support from Novartis, Merck, Roche and Amgen, Consulting fees from Eli Lilly, Amgen, Zosano, Radius, Nycomed. doi:10.1016/j.bone.2012.02.148
OPC09 Effects of alendronate and risedronate on bone material properties in actively forming trabecular bone surfaces B. Hofstettera, S. Gamsjaegera,⁎, R.J. Phippsb, R.R. Reckerc, F.H. Ebetinod, K. Klaushofera, E.P. Paschalisa
S55
a
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Heinrich Collin Str. 30, A-1140, Vienna, Austria b University School of Pharmacy Husson, Bangor, USA c Osteoporosis Research Center, Creighton University, Omaha, USA d Warner Chilcott, Dundalk, Ireland
Abstract: In the present work we examined the effect of alendronate (ALN) and risedronate (RIS) treatment on bone material properties by Raman and Fourier Transform Infrared Imaging (FTIR) microspectroscopic analysis at actively bone forming trabecular surfaces. At 8 study sites, women were identified who had postmenopausal osteoporosis (PMO), were at least 5 year postmenopause and had been on long-term therapy (either 3–5 or N 5 years) with daily or weekly ALN or RIS. Following standard tetracycline labeling, biopsies were collected from 102 women (33 were treated with ALN for 3–5 years (ALN-3), 35 with ALN for N5 years (ALN-5), 26 with RIS for 3–5 years (RIS-3) and 8 with RIS for N 5 years (RIS-5)) and analyzed at anatomical areas of similar tissue age in bone forming areas (determined from the fluorescent labels). The parameters measured were mineral to matrix ratio (corresponding to ash weight), relative proteoglycan content (regulating mineralization initiation), mineral maturity (indicative of the mineral crystallite chemistry and stoichiometry, and having a direct bearing on crystallite shape and size), and the ratio of two of the major enzymatic collagen cross-links (pyridinoline/divalent). No significant differences in mineral/matrix ratio amongst the 4 groups were evident. Relative proteoglycan content was significantly lower in the patients receiving RIS long-term (RIS-5) compared to patients receiving long term ALN therapy (ALN-5). Similarly, this was significantly lower in the long-term RIS users compared to the short-term users (RIS-3 vs RIS-5). Mineral maturity/crystallinity as determined from Raman analysis was significantly lower in the RIS-3 and RIS-5 groups compared to the ALN-3 and ALN-5 groups, respectively. The pyr/divalent collagen cross-link ratio was significantly lower in RIS compared to ALN at both 3–5 and 5 years; additionally, the RIS-5 group had significantly lower values compared to the RIS-3 group. The results of the present study indicate that ALNand RIS exert differential effects on the intrinsic bone material properties at actively bone forming trabecular surfaces. This suggests that the two drugs achieve their antifracture efficacy via different mechanisms or influence the same mechanisms differently (e.g. bone affinity and enzyme inhibition). Additionally, these results emphasize the need to understand quantitative and qualitative effects on bone formation when evaluating drug performance. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: B. Hofstetter: None Declared, S. Gamsjaeger: none declared, R. Phipps Employee of Alliance for Better Bone Health, R. Recker: none declared, F. Ebetino Employee of Warner Chilcott, K. Klaushofer: none declared, E. Paschalis: none declared. doi:10.1016/j.bone.2012.02.149
OPC10 High physical capacity in young adulthood reduces the risk of fracture later in life P. Nordströma,⁎, H. Sievänenb, Y. Gustafsona, N. Pedersenc, A. Nordströmd a Geriatric Medicine, Umeå, Sweden b Health Promotion Research, Tampere, Finland c Karolinska Institute, Stockholm, Sweden d Rehabilitation Medicine, Umeå, Sweden Abstract: Context: Despite the impact of fractures on patients' quality of life and the healthcare burden, little is known about the influence of physical fitness in young adulthood on fracture risk later in life. Objective We investigated whether high aerobic fitness and muscle strength in young adulthood reduced the risk of low-energy fracture later in life in men. Design, setting, and participants: During national conscription tests conducted in Sweden in 1969–1978, the aerobic fitness and isometric muscle strength of 435,445 men (mean age, 18.5 years) were evaluated. Main outcome measure: Data on men who sustained low-energy fractures after the age of 40 years were collected from national registers. Results: During a median follow-up period of 35 years (range, 11–41 years), 8030 subjects sustained at least one low-energy fracture. After adjusting for potential confounders, the risk of low-energy fracture was 1.8 times higher (95% confidence interval, 1.6–2.1) and that of hip fracture was 2.7 times higher (95% confidence interval, 1.6–4.7) among men in the lowest decile of aerobic fitness than among those in the highest decile. The risk of low-energy fracture was also 1.4–1.5 times higher among men in the lowest deciles of knee extension strength, grip strength, and elbow flexion strength (p b 0.001 for all), compared with those in the highest deciles. Conclusion: The results of the present study show that low aerobic fitness and muscle strength in young adulthood were associated with an elevated risk of low-energy fracture more than 30 years later in men.