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Association of Bisphosphonate Therapy With Incident of Lower Extremity Fractures in Persons With Spinal Cord Injuries or Disorders

Published:January 17, 2020DOI:https://doi.org/10.1016/j.apmr.2019.12.010

      Abstract

      Objective

      To investigate the association between prescriptions for bisphosphonates; calcium and vitamin D supplements; and receipt of dual-energy x-ray absorptiometry (DXA) screening, and incident fracture risk in men and women with a spinal cord injury (SCI) or disorder (SCID).

      Design

      Propensity-matched case-control analyses.

      Setting

      United States Veterans Affairs (VA) facilities.

      Participants

      A total of 7989 men and 849 women with an SCID included in VA administrative databases between October 1, 2005 and October 1, 2015 were identified (N=8838). Cases included 267 men and 59 women with a bisphosphonate prescription propensity matched with up to 4 controls.

      Interventions

      Not applicable.

      Main Outcome Measures

      Incident lower extremity fractures.

      Results

      There was no significant association between prescriptions for bisphosphonates and incident lower extremity fractures in men (odds ratio [OR], 1.04; 95% confidence interval [CI], 0.62-1.77) or women (OR, 1.02; 95% CI, 0.28-3.75). In men, similar null associations were seen among those who were adherent to bisphosphonate therapy (OR, 1.25; 95% CI, 0.73-2.16), were concomitant users of vitamin D and calcium and a bisphosphonate (OR, 1.05; 95% CI, 0.57-1.96), had more than 1 fracture on different dates during the study period (OR, 0.13; 95% CI, 0.02-1.16) and in those who had undergone DXA testing prior to the date of the bisphosphonate prescription and incident fracture (OR, 1.26; 95% CI, 0.69-2.32).

      Conclusions

      In men with a traumatic SCI and women with a traumatic SCID, bisphosphonate therapies for osteoporosis do not appear to significantly affect fracture risk. Adequately powered randomized controlled trials are needed to definitively demonstrate efficacy of bisphosphonates for fracture prevention in this population. There is a compelling need to identify new medications to prevent fractures in this high-risk population.

      Keywords

      List of abbreviations:

      ARC (allocation resource center), CI (confidence interval), DXA (dual-energy x-ray absorptiometry), FY (fiscal year), ICD-9 (International Classification of Diseases, Ninth Revision), LE (lower extremity), OR (odds ratio), SCD (spinal cord dysfunction), SCI (spinal cord injury), SCID (spinal cord injury disorder), VA (Veterans Affairs), VHA (Veterans Health Administration)
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      References

        • Garland D.E.
        • Adkins R.H.
        • Kushwaha V.
        • Stewart C.
        Risk factors for osteoporosis at the knee in the spinal cord injury population.
        J Spinal Cord Med. 2004; 27: 202-206
        • Rush T.M.
        • Kritz-Silverstein D.
        • Laughlin G.A.
        • Fung T.T.
        • Barrett-Connor E.
        • McEvoy L.K.
        Association between dietary sodium intake and cognitive function in older adults.
        J Nutr Health Aging. 2017; 21: 276-283
        • Abderhalden L.
        • Weaver F.M.
        • Bethel M.
        • et al.
        Dual-energy X-ray absorptiometry and fracture prediction in patients with spinal cord injuries and disorders.
        Osteoporos Int. 2017; 28: 925-934
        • Carbone L.D.
        • Chin A.S.
        • Burns S.P.
        • et al.
        Mortality after lower extremity fractures in men with spinal cord injury.
        J Bone Miner Res. 2014; 29: 432-439
        • Carbone L.
        • Chin A.S.
        • Lee T.A.
        • et al.
        The association of anticonvulsant use with fractures in spinal cord injury.
        Am J Phys Med Rehabil. 2013; 92: 1037-1046
        • Harris S.T.
        • Watts N.B.
        • Genant H.K.
        • et al.
        Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.
        JAMA. 1999; 282: 1344-1352
        • Black D.M.
        • Cummings S.R.
        • Karpf D.B.
        • et al.
        Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group.
        Lancet. 1996; 348: 1535-1541
        • Black D.M.
        • Delmas P.D.
        • Eastell R.
        • et al.
        Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.
        N Engl J Med. 2007; 356: 1809-1822
        • Zleik N.
        • Weaver F.
        • Harmon R.L.
        • et al.
        Prevention and management of osteoporosis and osteoporotic fractures in persons with a spinal cord injury or disorder: a systematic scoping review.
        J Spinal Cord Med. 2018; : 1-25
        • Chang K.V.
        • Hung C.Y.
        • Chen W.S.
        • Lai M.S.
        • Chien K.L.
        • Han D.S.
        Effectiveness of bisphosphonate analogues and functional electrical stimulation on attenuating post-injury osteoporosis in spinal cord injury patients: a systematic review and meta-analysis.
        PLoS One. 2013; 8e81124
        • Bryson J.E.
        • Gourlay M.L.
        Bisphosphonate use in acute and chronic spinal cord injury: a systematic review.
        J Spinal Cord Med. 2009; 32: 215-225
        • Zehnder Y.
        • Risi S.
        • Michel D.
        • et al.
        Prevention of bone loss in paraplegics over 2 years with alendronate.
        J Bone Miner Res. 2004; 19: 1067-1074
        • Moran de Brito C.M.
        • Battistella L.R.
        • Saito E.T.
        • Sakamoto H.
        Effect of alendronate on bone mineral density in spinal cord injury patients: a pilot study.
        Spinal Cord. 2005; 43: 341-348
        • Bubbear J.S.
        • Gall A.
        • Middleton F.R.
        • Ferguson-Pell M.
        • Swaminathan R.
        • Keen R.W.
        Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury.
        Osteoporos Int. 2011; 22: 271-279
        • Bubbear J.S.
        • Gall A.
        • Middleton F.R.
        • Shah V.
        • Keen R.W.
        Use of alendronate in management of osteoporosis following spinal cord injury: a report of 4 cases.
        J Bone Miner Res. 2004; 19: 1046
        • Sniger W.
        • Garshick E.
        Alendronate increases bone density in chronic spinal cord injury: a case report.
        Arch Phys Med Rehabil. 2002; 83: 139-140
        • Gilchrist N.L.
        • Frampton C.M.
        • Acland R.H.
        • et al.
        Alendronate prevents bone loss in patients with acute spinal cord injury: a randomized, double-blind, placebo-controlled study.
        J Clin Endocrinol Metab. 2007; 92: 1385-1390
        • Bauman W.A.
        • Cirnigliaro C.M.
        • La Fountaine M.F.
        • Martinez L.
        • Kirshblum S.C.
        • Spungen A.M.
        Zoledronic acid administration failed to prevent bone loss at the knee in persons with acute spinal cord injury: an observational cohort study.
        J Bone Miner Metab. 2015; 33: 410-421
        • Smith B.M.
        • Evans C.T.
        • Ullrich P.
        • et al.
        Using VA data for research in persons with spinal cord injuries and disorders: lessons from SCI QUERI.
        J Rehabil Res Dev. 2010; 47: 679-688
        • Curtis J.R.
        • Cai Q.
        • Wade S.W.
        • et al.
        Osteoporosis medication adherence: physician perceptions vs. patients' utilization.
        Bone. 2013; 55: 1-6
        • Bethel M.
        • Weaver F.M.
        • Bailey L.
        • et al.
        Risk factors for osteoporotic fractures in persons with spinal cord injuries and disorders.
        Osteoporos Int. 2016; 27: 3011-3021
        • Leon A.C.
        • Hedeker D.
        Propensity score stratification for observational comparison of repeated binary outcomes.
        Stat Interface. 2011; 4: 489-498
        • Logan Jr., W.C.
        • Sloane R.
        • Lyles K.W.
        • Goldstein B.
        • Hoenig H.M.
        Incidence of fractures in a cohort of veterans with chronic multiple sclerosis or traumatic spinal cord injury.
        Arch Phys Med Rehabil. 2008; 89: 237-243
        • Goenka S.
        • Sethi S.
        • Pandey N.
        • Joshi M.
        • Jindal R.
        Effect of early treatment with zoledronic acid on prevention of bone loss in patients with acute spinal cord injury: a randomized controlled trial.
        Spinal Cord. 2018; 56: 1207-1211
        • Ott S.M.
        Osteoporosis in women with spinal cord injuries.
        Phys Med Rehabil Clin N Am. 2001; 12: 111-131
        • Nayak S.
        • Greenspan S.L.
        Osteoporosis treatment efficacy for men: a systematic review and meta-analysis.
        J Am Geriatr Soc. 2017; 65: 490-495
        • Zhou J.
        • Wang T.
        • Zhao X.
        • Miller D.R.
        • Zhai S.
        Comparative efficacy of bisphosphonates to prevent fracture in men with osteoporosis: a systematic review with network meta-analyses.
        Rheumatol Ther. 2016; 3: 117-128
        • Qin W.
        • Bauman W.A.
        • Cardozo C.
        Bone and muscle loss after spinal cord injury: organ interactions.
        Ann N Y Acad Sci. 2010; 1211: 66-84
        • Battaglino R.A.
        • Lazzari A.A.
        • Garshick E.
        • Morse L.R.
        Spinal cord injury-induced osteoporosis: pathogenesis and emerging therapies.
        Curr Osteoporos Rep. 2012; 10: 278-285
        • Rachner T.D.
        • Khosla S.
        • Hofbauer L.C.
        Osteoporosis: now and the future.
        Lancet. 2011; 377: 1276-1287
        • Klotzbuecher C.M.
        • Ross P.D.
        • Landsman P.B.
        • Abbott 3rd, T.A.
        • Berger M.
        Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis.
        J Bone Miner Res. 2000; 15: 721-739
        • Akhigbe T.
        • Chin A.S.
        • Svircev J.N.
        • et al.
        A retrospective review of lower extremity fracture care in patients with spinal cord injury.
        J Spinal Cord Med. 2015; 38: 2-9
        • Jansen J.P.
        • Bergman G.J.
        • Huels J.
        • Olson M.
        The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis.
        Semin Arthritis Rheum. 2011; 40: 275-284
        • Russell R.G.
        Bisphosphonates: from bench to bedside.
        Ann N Y Acad Sci. 2006; 1068: 367-401
        • Wu X.
        • Wei D.
        • Sun B.
        • Wu X.N.
        Poor medication adherence to bisphosphonates and high self-perception of aging in elderly female patients with osteoporosis.
        Osteoporos Int. 2016; 27: 3083-3090
        • Caro J.J.
        • Ishak K.J.
        • Huybrechts K.F.
        • Raggio G.
        • Naujoks C.
        The impact of compliance with osteoporosis therapy on fracture rates in actual practice.
        Osteoporos Int. 2004; 15: 1003-1008
        • Deane A.
        • Constancio L.
        • Fogelman I.
        • Hampson G.
        The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis.
        BMC Musculoskelet Disord. 2007; 8: 3
        • Adami S.
        • Giannini S.
        • Bianchi G.
        • et al.
        Vitamin D status and response to treatment in postmenopausal osteoporosis.
        Osteoporos Int. 2009; 20: 239-244
        • Bourke S.
        • Bolland M.J.
        • Grey A.
        • et al.
        The impact of dietary calcium intake and vitamin D status on the effects of zoledronate.
        Osteoporos Int. 2013; 24: 349-354
        • Silveira S.L.
        • Winter L.L.
        • Clark R.
        • Ledoux T.
        • Robinson-Whelen S.
        Baseline dietary intake of individuals with spinal cord injury who are overweight or obese.
        J Acad Nutr Diet. 2019; 119: 301-309
        • Oleson C.V.
        • Patel P.H.
        • Wuermser L.A.
        Influence of season, ethnicity, and chronicity on vitamin D deficiency in traumatic spinal cord injury.
        J Spinal Cord Med. 2010; 33: 202-213
        • Morse L.R.
        • Giangregorio L.
        • Battaglino R.A.
        • et al.
        VA-based survey of osteoporosis management in spinal cord injury.
        PM R. 2009; 1: 240-244
        • Flueck J.L.
        • Perret C.
        Vitamin D deficiency in individuals with a spinal cord injury: a literature review.
        Spinal Cord. 2017; 55: 428-434
        • Eastell R.
        • Black D.M.
        • Boonen S.
        • et al.
        Effect of once-yearly zoledronic acid five milligrams on fracture risk and change in femoral neck bone mineral density.
        J Clin Endocrinol Metab. 2009; 94: 3215-3225
        • Appelman-Dijkstra N.M.
        • Papapoulos S.E.
        Prevention of incident fractures in patients with prevalent fragility fractures: current and future approaches.
        Best Pract Res Clin Rheumatol. 2013; 27: 805-820
        • Weaver F.M.
        • Le B.
        • Ray C.
        • Miskevics S.
        • Gonzalez B.
        • Carbone L.D.
        Predicting osteoporosis medication receipt in veterans with a spinal cord injury: a retrospective cohort study.
        J Spinal Cord Med. 2019; : 1-8
        • Hatch M.N.
        • Raad J.
        • Suda K.
        • Stroupe K.T.
        • Hon A.J.
        • Smith B.M.
        Evaluating the use of Medicare Part D in the spinal cord injury/disorder veteran population.
        Arch Phys Med Rehabil. 2018; 99: 1099-1107
        • Boonen S.
        • Reginster J.Y.
        • Kaufman J.M.
        • et al.
        Fracture risk and zoledronic acid therapy in men with osteoporosis.
        N Engl J Med. 2012; 367: 1714-1723
        • Orwoll E.
        • Ettinger M.
        • Weiss S.
        • et al.
        Alendronate for the treatment of osteoporosis in men.
        N Engl J Med. 2000; 343: 604-610
        • Lucas R.
        • Rocha O.
        • Bastos J.
        • Costa L.
        • Barros H.
        • Lunet N.
        Pharmacological management of osteoporosis and concomitant calcium supplementation in a Portuguese urban population: the EpiPorto study (2005-2007).
        Clin Exp Rheumatol. 2009; 27: 47-53
        • Stafford R.S.
        • Drieling R.L.
        • Johns R.
        • Ma J.
        National patterns of calcium use in osteoporosis in the United States.
        J Reprod Med. 2005; 50: 885-890
        • Porras A.G.
        • Holland S.D.
        • Gertz B.J.
        Pharmacokinetics of alendronate.
        Clin Pharmacokinet. 1999; 36: 315-328