Skip to main content
Erschienen in: Osteoporosis International 1/2013

01.01.2013 | Original Article

Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment: a National Prescription registry study

verfasst von: B. Abrahamsen, K. H. Rubin, P. A. Eiken, R. Eastell

Erschienen in: Osteoporosis International | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

Summary

Antiresorptive treatment reduces the risk of fractures, but most patients remain at elevated risk. We used health registers to identify predictors of new major osteoporotic fractures in patients adhering to alendronate. Risk factors showed a different pattern than in the general population and included dementia, ulcer disease, and Parkinson’s disease.

Introduction

Antiresorptives reduce the excess risk of fractures in patients with osteoporosis, but most patients remain at elevated risk. In some countries, patients must sustain fractures while on bisphosphonate (BP) treatment to qualify for more expensive treatment. It is unclear if patients who fracture on BP can be viewed as a distinct subgroup.

Methods

The National Prescription registry was used to identify 38,088 new alendronate users. The outcome was major osteoporotic fractures 6+ months after filling the first prescription in patients with a medication possession ratio > 80 %.

Results

One thousand and seventy-two (5.5 %) patients sustained major osteoporotic fractures. The risk increased with age and was lower in men. The most important risk factor was the number of comedications (hazard ratio (HR) 1.04, 95 % CI 1.03–1.06, for each drug). Dementia (HR 1.81, 95 % CI 1.18–2.78), prior fracture (one: HR 1.17, 95 % CI 1.02–1.34; multiple: HR 1.34, 95 % CI 1.08–1.67), and ulcer disease (HR 1.45, 95 % CI 1.04–2.03) also increased the risk. Diabetes did not influence fracture risk, nor did rheumatic disorders. The risk was lower in glucocorticoid users (HR 0.78, 95 % CI 0.65–0.93).

Conclusion

Risk factors while adhering to BP show a somewhat different pattern than that of the general population and FRAX. Ulcer disease and dementia may impair the ability to use the medications correctly. Though this is an observational study and associations may not be causal, it may be prudent to include dementia, ulcer disease, and Parkinson’s disease to capture the risk of fractures on treatment. Lower risk in patients treated with glucocorticoids and in men probably reflects a lower treatment threshold related to guidelines.
Literatur
1.
Zurück zum Zitat Hochberg MC, Thompson DE, Black DM, Quandt SA, Cauley J, Geusens P et al (2005) Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures. J Bone Miner Res 20:971–976PubMedCrossRef Hochberg MC, Thompson DE, Black DM, Quandt SA, Cauley J, Geusens P et al (2005) Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures. J Bone Miner Res 20:971–976PubMedCrossRef
2.
Zurück zum Zitat Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541PubMedCrossRef Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541PubMedCrossRef
3.
Zurück zum Zitat Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH et al (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443PubMedCrossRef Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH et al (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group. N Engl J Med 333:1437–1443PubMedCrossRef
5.
Zurück zum Zitat Clement FM, Harris A, Yong K, Lee KM, Manns BJ (2009) Using effectiveness and cost-effectiveness to make drug coverage decisions. JAMA 302:1437–1443PubMedCrossRef Clement FM, Harris A, Yong K, Lee KM, Manns BJ (2009) Using effectiveness and cost-effectiveness to make drug coverage decisions. JAMA 302:1437–1443PubMedCrossRef
6.
Zurück zum Zitat Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA (2012) Does osteoporosis therapy invalidate FRAX for fracture prediction? JBMR. doi:10.1002/jbmr.1582 Leslie WD, Lix LM, Johansson H, Oden A, McCloskey E, Kanis JA (2012) Does osteoporosis therapy invalidate FRAX for fracture prediction? JBMR. doi:10.​1002/​jbmr.​1582
7.
Zurück zum Zitat Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA et al (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 280:2077–2082PubMedCrossRef Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA et al (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 280:2077–2082PubMedCrossRef
8.
Zurück zum Zitat Inderjeeth CA, Chan K, Kwan K, Lai M (2012) Time to onset of efficacy in fracture reduction with current anti-osteoporosis treatments. J Bone Miner Metab. doi:10.1007/s00774-012-0349-1 Inderjeeth CA, Chan K, Kwan K, Lai M (2012) Time to onset of efficacy in fracture reduction with current anti-osteoporosis treatments. J Bone Miner Metab. doi:10.​1007/​s00774-012-0349-1
9.
Zurück zum Zitat Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC et al (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139PubMedCrossRef Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi JC et al (2005) Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care 43:1130–1139PubMedCrossRef
10.
Zurück zum Zitat Eastell R, Black DM, Boonen S, Adami S, Felsenberg D, Lippuner K et al (2009) Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density. J Clin Endocrinol Metab 94:3215–3225PubMedCrossRef Eastell R, Black DM, Boonen S, Adami S, Felsenberg D, Lippuner K et al (2009) Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density. J Clin Endocrinol Metab 94:3215–3225PubMedCrossRef
11.
Zurück zum Zitat Eastell R, Vrijens B, Cahall DL, Ringe JD, Garnero P, Watts NB (2011) Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J Bone Min Res: Off J Am Soc Bone Min Res 26:1662–1669. doi:10.1002/jbmr.342 CrossRef Eastell R, Vrijens B, Cahall DL, Ringe JD, Garnero P, Watts NB (2011) Bone turnover markers and bone mineral density response with risedronate therapy: relationship with fracture risk and patient adherence. J Bone Min Res: Off J Am Soc Bone Min Res 26:1662–1669. doi:10.​1002/​jbmr.​342 CrossRef
12.
Zurück zum Zitat Siris ES, Chen YT, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE et al (2004) Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 164:1108–1112PubMedCrossRef Siris ES, Chen YT, Abbott TA, Barrett-Connor E, Miller PD, Wehren LE et al (2004) Bone mineral density thresholds for pharmacological intervention to prevent fractures. Arch Intern Med 164:1108–1112PubMedCrossRef
15.
Zurück zum Zitat Abrahamsen B, Brixen K (2009) Mapping the prescriptiome to fractures in men–a national analysis of prescription history and fracture risk. Osteoporos Int 20:585–597PubMedCrossRef Abrahamsen B, Brixen K (2009) Mapping the prescriptiome to fractures in men–a national analysis of prescription history and fracture risk. Osteoporos Int 20:585–597PubMedCrossRef
16.
Zurück zum Zitat Eom C-S, Lee H-K, Ye S, Park SM, Cho K-H (2012) Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. JBMR 27:1186–1195. doi:10.1002/jbmr.1554 CrossRef Eom C-S, Lee H-K, Ye S, Park SM, Cho K-H (2012) Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. JBMR 27:1186–1195. doi:10.​1002/​jbmr.​1554 CrossRef
17.
Zurück zum Zitat Vestergaard P, Rejnmark L, Mosekilde L (2008) Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcif Tissue Int 82:92–101PubMedCrossRef Vestergaard P, Rejnmark L, Mosekilde L (2008) Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcif Tissue Int 82:92–101PubMedCrossRef
18.
Zurück zum Zitat Vestergaard P, Rejnmark L, Mosekilde L (2007) Fracture risk associated with parkinsonism and anti-Parkinson drugs. Calcif Tissue Int 81:153–161PubMedCrossRef Vestergaard P, Rejnmark L, Mosekilde L (2007) Fracture risk associated with parkinsonism and anti-Parkinson drugs. Calcif Tissue Int 81:153–161PubMedCrossRef
19.
Zurück zum Zitat Fink HA, Kuskowski MA, Orwoll ES, Cauley JA, Ensrud KE (2005) Association between Parkinson’s disease and low bone density and falls in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 53:1559–1564PubMedCrossRef Fink HA, Kuskowski MA, Orwoll ES, Cauley JA, Ensrud KE (2005) Association between Parkinson’s disease and low bone density and falls in older men: the osteoporotic fractures in men study. J Am Geriatr Soc 53:1559–1564PubMedCrossRef
20.
Zurück zum Zitat Abrahamsen B, Eiken P, Eastell R (2011) Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med Abrahamsen B, Eiken P, Eastell R (2011) Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med
21.
Zurück zum Zitat Figura N, Gennari L, Merlotti D, Lenzi C, Campagna S, Franci B et al (2005) Prevalence of helicobacter pylori infection in male patients with osteoporosis and controls. Dig Dis Sci 50:847–852PubMedCrossRef Figura N, Gennari L, Merlotti D, Lenzi C, Campagna S, Franci B et al (2005) Prevalence of helicobacter pylori infection in male patients with osteoporosis and controls. Dig Dis Sci 50:847–852PubMedCrossRef
22.
Zurück zum Zitat Goerss JB, Kim CH, Atkinson EJ, Eastell R, O’Fallon WM, Melton LJ III (1992) Risk of fractures in patients with pernicious anemia. J Bone Miner Res 7:573–579PubMedCrossRef Goerss JB, Kim CH, Atkinson EJ, Eastell R, O’Fallon WM, Melton LJ III (1992) Risk of fractures in patients with pernicious anemia. J Bone Miner Res 7:573–579PubMedCrossRef
24.
Zurück zum Zitat Rejnmark L, Vestergaard P, Mosekilde L (2005) Reduced fracture risk in users of thiazide diuretics. Calcif Tissue Int 76:167–175PubMedCrossRef Rejnmark L, Vestergaard P, Mosekilde L (2005) Reduced fracture risk in users of thiazide diuretics. Calcif Tissue Int 76:167–175PubMedCrossRef
25.
Zurück zum Zitat Rejnmark L, Vestergaard P, Pedersen AR, Heickendorff L, Andreasen F, Mosekilde L (2003) Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women. Eur J Clin Invest 33:41–50PubMedCrossRef Rejnmark L, Vestergaard P, Pedersen AR, Heickendorff L, Andreasen F, Mosekilde L (2003) Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women. Eur J Clin Invest 33:41–50PubMedCrossRef
26.
Zurück zum Zitat Jamal SA, Hamilton CJ, Eastell R, Cummings SR (2011) Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA 305:800–807PubMedCrossRef Jamal SA, Hamilton CJ, Eastell R, Cummings SR (2011) Effect of nitroglycerin ointment on bone density and strength in postmenopausal women: a randomized trial. JAMA 305:800–807PubMedCrossRef
27.
Zurück zum Zitat Rejnmark L, Vestergaard P, Mosekilde L (2006) Decreased fracture risk in users of organic nitrates: a nationwide case-control study. J Bone Miner Res 21:1811–1817PubMedCrossRef Rejnmark L, Vestergaard P, Mosekilde L (2006) Decreased fracture risk in users of organic nitrates: a nationwide case-control study. J Bone Miner Res 21:1811–1817PubMedCrossRef
28.
Zurück zum Zitat Pouwels S, Lalmohamed A, van Staa T, Cooper C, Souverein P, Leufkens HG et al (2010) Use of organic nitrates and the risk of hip fracture: a population-based case-control study. J Clin Endocrinol Metab 95:1924–1931. doi:10.1210/jc.2009-2342 PubMedCrossRef Pouwels S, Lalmohamed A, van Staa T, Cooper C, Souverein P, Leufkens HG et al (2010) Use of organic nitrates and the risk of hip fracture: a population-based case-control study. J Clin Endocrinol Metab 95:1924–1931. doi:10.​1210/​jc.​2009-2342 PubMedCrossRef
29.
Zurück zum Zitat Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T et al (2011) International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49:1271–1274PubMedCrossRef Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T et al (2011) International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49:1271–1274PubMedCrossRef
30.
Zurück zum Zitat Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRef Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY et al (2001) Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441PubMedCrossRef
Metadaten
Titel
Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment: a National Prescription registry study
verfasst von
B. Abrahamsen
K. H. Rubin
P. A. Eiken
R. Eastell
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 1/2013
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-2184-6

Weitere Artikel der Ausgabe 1/2013

Osteoporosis International 1/2013 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.