Top

Osteoporosis International

Published in:

01-02-2015 | Original Article

Predictors of re-fracture amongst patients managed within a secondary fracture prevention program: a 7-year prospective study

Authors: K. Ganda, A. Schaffer, M. J. Seibel

Published in: Osteoporosis International | Issue 2/2015

Abstract

Summary

This 7-year prospective observational study determined the predictors of re-fracture amongst 234 patients managed within a Secondary Fracture Prevention programme. Poor compliance, multiple co-morbidities, corticosteroid therapy, low hip bone mineral density (BMD) or low body weight were all significantly associated with re-fracture in patients commenced on long-term anti-resorptive therapy.

Introduction

Risk factors for osteoporotic fracture amongst treatment-naïve patients are well established. In contrast, predictors of re-fracture in patients optimally managed within a Secondary Fracture Prevention (SFP) programme are ill-defined.

Methods

This prospective observational study included 234 subjects with incident osteoporotic fractures managed long-term by the Concord SFP programme. Using Cox proportional hazards models, predictors of re-fracture were analysed separately for patients commenced on specific pharmacotherapy (group 1, N = 171) and subjects receiving calcium and/or vitamin D supplements only (group 2, N = 63). Relevant anthropometric, clinical and technical data were documented at each visit. Compliance and persistence were analysed as time-varying covariates.

Results

During a mean follow-up of 5.2 (range 3.5–7.3) years, 20.9 % of all subjects re-fractured (26.3 % in group 1, 6.3 % in group 2). Multivariate predictors of re-fracture in group 1 were significant co-morbidity (HR 2.04 if >3, 95 % CI 1.10–3.79, p = 0.024), corticosteroid use (HR 1.75, 95 % CI 1.12–2.73, p = 0.013) and total hip BMD (HR 1.36 per 0.1 g/cm² decrease, 95 % CI 1.08–1.70, p = 0.008). In contrast, gender, prevalent fractures and lumbar spine BMD were not associated with re-fracture. Amongst patients with complete compliance data, a medication possession ratio of ≤ 50 % (HR 3.36, 95 % CI 1.32–8.53, p = 0.011) and low body weight (HR 1.04 per 1-kg decrease, 95 % CI 1.003–1.08, p = 0.032) were significantly associated with re-fracture.

Conclusions

Amongst patients managed within a dedicated SFP programme, poor compliance, multiple co-morbidities, corticosteroid therapy, low hip BMD or low body weight are all associated with increased risk of re-fracture. This subgroup of patients therefore require intensive management including strategies to improve compliance.

World Health Organisation (2001) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Report of a WHO Study Group. Geneva: WHO, 1994 (Technical Report Series 843). J Am Med Assoc 285:785–795CrossRef

Kanis JA, Johnell O, Oden A (2000) Long-term risk of osteoporotic fracture in Malmo. Osteoporos Int 11:669–674PubMedCrossRef

Nguyen ND, Ahlborg HG, Center JR, Eisman JA, Nguyen TV (2007) Residual lifetime risk of fractures in women and men. J Bone Miner Res 22:781–788PubMedCrossRef

Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Centre JR (2009) Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. J Am Med Assoc 301:513–521CrossRef

Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA (1999) Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878–882PubMedCrossRef

Center J, Bliuc D, Nguyen TV, Eisman J (2007) Risk of subsequent fracture after low-trauma fracture in men and women. J Am Med Assoc 297:387–394CrossRef

Langsetmo L, Goltzman D, Kovacs CS, Adachi JD, Hanley DA, Kreiger N, Josse R, Papaioannou A, Olszynski WP, Jamal SA (2009) Repeat low-trauma fractures occur frequently among men and women who have osteopenic BMD. J Bone Miner Res 24:1515–1522PubMedCrossRef

van Geel TA, van Helden S, Geusens PP, Winkens B, Dinant GJ (2009) Clinical subsequent fractures cluster in time after first fractures. Ann Rheum Dis 68:99–102PubMedCrossRef

Ganda K, Schaffer A, Pearson S, Seibel MJ (2014) Compliance and persistence to oral bisphosphonate therapy following initiation within a secondary fracture prevention program: a randomised controlled trial of specialist vs. non-specialist management. Osteoporos Int 25:1345–1355

10.

Sale JEM, Beaton D, Posen J, Elliot-Gibson V, Bogoch E (2011) Systematic review on interventions to improve osteoporosis investigation and treatment in fragility fracture patients. Osteoporos Int 22:2067–2082PubMedCrossRef

11.

Cooper MS, Palmer AJ, Seibel MJ (2012) Cost-effectiveness of the Concord Minimal Trauma Fracture Liaison service, a prospective, controlled fracture prevention study. Osteoporos Int 23:97–107PubMedCrossRef

12.

Lih A, Nandapalan H, Kim M, Yap C, Lee P, Ganda K, Seibel MJ (2011) Targeted intervention reduces refracture rates in patients with incident non-vertebral osteoporotic fractures: a 4-year prospective controlled study. Osteoporos Int 22:849–858PubMedCrossRef

13.

Kanis JA (2002) Diagnosis of osteoporosis and assessment of fracture risk. Lancet 359:1929–1936PubMedCrossRef

14.

Genant HK, Grampp S, Gluer CC, Faulkner KG, Jergas M, Engelke K, Hagiwara S, Van Kuijk C (1994) Universal standardization for dual x-ray absorptiometry: patient and phantom cross-calibration results. J Bone Miner Res 9:1503–1514PubMedCrossRef

15.

Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward’s triangle. Osteoporos Int 12:438–444PubMedCrossRef

16.

Ganda K, Puech M, Chen JS, Speerin R, Bleasel J, Center JR, Eisman JA, March L, Seibel MJ (2013) Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis. Osteoporos Int 24:393–406

17.

(2010) Clinical guideline for the prevention and treatment of osteoporosis in postmenopausal women and older men. The Royal Australian College of General Practitioners, South Melbourne

18.

Cramer JA, Roy A, Burrell A, Fairchild CJ, Fuldeore MJ, Ollendorf DA, Wong PK (2008) Medication compliance and persistence: terminology and definitions. Value Health 11:44–47PubMedCrossRef

19.

Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822PubMedCrossRef

20.

Black DM, Thompson DE, Bauer DC, Ensrud K, Musliner T, Hochberg MC, Nevitt MC, Suryawanshi S, Cummings SR (2000) Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab 85:4118–4124PubMedCrossRef

21.

Harrington JT, Ste-Marie LG, Brandi ML, Civitelli R, Fardellone P, Grauer A, Barton I, Boonen S (2004) Risedronate rapidly reduces the risk for nonvertebral fractures in women with postmenopausal osteoporosis. Calcif Tissue Int 74:129–135PubMedCrossRef

22.

Cranney A, Papaioannou A, Zytaruk N, Hanley D, Adachi J, Goltzman D, Murray T, Hodsman A (2006) Parathyroid hormone for the treatment of osteoporosis: a systematic review. CMAJ 175:52–59PubMedCentralPubMedCrossRef

23.

Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765PubMedCrossRef

24.

Guyatt GH, Cranney A, Griffith L, Walter S, Krolicki N, Favus M, Rosen C (2002) Summary of meta-analyses of therapies for postmenopausal osteoporosis and the relationship between bone density and fractures. Endocrinol Metab Clin N Am 31:659–679CrossRef

25.

Stevenson M, Davis S, Lloyd-Jones M, Beverley C (2007) The clinical effectiveness and cost-effectiveness of strontium ranelate for the prevention of osteoporotic fragility fractures in postmenopausal women. Health Technol Assess 11:1–134PubMedCrossRef

26.

Dell R, Greene D, Schelkun SR, Williams K (2008) Osteoporosis disease management: the role of the orthopaedic surgeon. J Bone Joint Surg Am 90(Suppl 4):188–194PubMedCrossRef

27.

Dell RM, Greene D, Anderson D, Williams K (2009) Osteoporosis disease management: what every orthopaedic surgeon should know. J Bone Joint Surg Am 91(Suppl 6):79–86PubMedCrossRef

28.

Diez-Perez A, Olmos JM, Nogues X et al (2012) Risk factors for prediction of inadequate response to antiresorptives. J Bone Miner Res 27:817–824PubMedCrossRef

29.

Abrahamsen B, Rubin KH, Eiken PA, Eastell R (2013) Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment: a National Prescription registry study. Osteoporos Int 24:321–328PubMedCrossRef

30.

Prieto-Alhambra D, Pages-Castella A, Wallace G, Javaid MK, Judge A, Nogues X, Arden NK, Cooper C, Diez-Perez A (2014) Predictors of fracture while on treatment with oral bisphosphonates: a population-based cohort study. J Bone Miner Res 29:268–274

31.

Diez-Perez A, Adachi JD, Adami S et al (2014) Risk factors for treatment failure with antiosteoporosis medication: the global longitudinal study of osteoporosis in women (GLOW). J Bone Miner Res 29:260–267PubMedCrossRef

32.

Adachi J, Lynch N, Middelhoven H, Hunjan M, Cowell W (2007) The association between compliance and persistence with bisphosphonate therapy and fracture risk: a review. BMC Musculoskelet Disord 8:97PubMedCentralPubMedCrossRef

33.

Imaz I, Zegarra P, Gonzalez-Enriquez J, Rubio B, Alcazar R, Amate JM (2010) Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int 21:1943–1951PubMedCrossRef

34.

Patrick AR, Brookhart MA, Losina E, Schousboe JT, Cadarette SM, Mogun H, Solomon DH (2010) The complex relation between bisphosphonate adherence and fracture reduction. J Clin Endocrinol Metab 95:3251–3259PubMedCentralPubMedCrossRef

35.

Sampalis JS, Adachi JD, Rampakakis E, Vaillancourt J, Karellis A, Kindundu C (2011) Long-term impact of adherence to oral bisphosphonates on osteoporotic fracture incidence. J Bone Miner Res

36.

Siris SE, Harris ST, Rosen C, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022PubMedCrossRef

37.

Cadarette SM, Solomon DH, Katz JN, Patrick AR, Brookhart MA (2011) Adherence to osteoporosis drugs and fracture prevention: no evidence of healthy adherer bias in a frail cohort of seniors. Osteoporos Int 22:943–954PubMedCentralPubMedCrossRef

38.

Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Breart G, Meunier PJ, Delmas PD (1996) Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study. J Bone Miner Res 11:1531–1538PubMedCrossRef

39.

Garnero P, Sornay-Rendu E, Claustrat B, Delmas PD (2000) Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res 15:1526–1536PubMedCrossRef

40.

van Daele PL, Seibel MJ, Burger H, Hofman A, Grobbee DE, van Leeuwen JP, Birkenhager JC, Pols H (1996) Case-control analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study. Br Med J 312:482–483CrossRef

41.

Meier C, Nguyen TV, Center JR, Seibel MJ, Eisman JA (2005) Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study. J Bone Miner Res 20:579–587PubMedCrossRef

42.

Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD, Fracture Intervention Trial Study G (2004) Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial. J Bone Miner Res 19:1250–1258PubMedCrossRef

43.

Sarkar S, Reginster JY, Crans GG, Diez-Perez A, Pinette KV, Delmas PD (2004) Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk. J Bone Miner Res 19:394–401PubMedCrossRef

44.

(2009) NSW re-fracture admission data 2002–2008 analysis discussion. Greater Metropolitan Clinical Taskforce Sydney

Title: Predictors of re-fracture amongst patients managed within a secondary fracture prevention program: a 7-year prospective study
Authors: K. Ganda
A. Schaffer
M. J. Seibel
Publication date: 01-02-2015
Publisher: Springer London
Published in: Osteoporosis International / Issue 2/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-014-2880-5

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Predictors of re-fracture amongst patients managed within a secondary fracture prevention program: a 7-year prospective study

Abstract

Summary

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2015

Subsequent fracture rates in a nationwide population-based cohort study with a 10-year perspective

Osteoporosis therapy: a novel insight from natural homeostatic system in the skeleton

Calcium metabolism, vitamin D and bone mineral density after bariatric surgery

Self-perceived facture risk: factors underlying women’s perception of risk for osteoporotic fractures: the Risk-Stratified Osteoporosis Strategy Evaluation study (ROSE)

Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT)

Increased risk of stroke among hip fracture patients: a nationwide cohort study