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Medications as a Risk Factor for Fragility Hip Fractures: A Systematic Review and Meta-analysis

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Abstract

Fragility hip fractures and their associated morbidity and mortality pose a global healthcare problem. Several pharmaceutical products have been postulated to alter bone architecture and contribute to fragility hip fractures. We searched four electronic databases from inception to September 2017. Inclusion criteria were the following: (1) adult patients with fragility hip fractures, (2) full text in English, (3) minimum one-year follow-up, and (4) reporting of at least one risk factor. To minimize heterogeneity among the studies, we performed subgroup analyses. Whenever heterogeneity remained significant, we employed random effect meta-analysis for data pooling. Thirty-eight studies were included, containing 1,244,155 subjects and 188,966 cases of fragility hip fractures. Following medications were significantly associated with fragility hip fractures: Antidepressants (OR 2.07, 95% CI 1.98–2.17), antiparkinsonian drugs (OR 2.21, 95% CI 1.15–4.24), antipsychotic drugs (OR 2.0, 95% CI 1.50–2.66), anxiolytic drugs (OR 1.44, 95% CI 1.19–1.75), benzodiazepines (OR 1.84, 95% CI 1.26–2.69), sedatives (OR 1.33, 95% CI 1.14–1.54), systemic corticosteroids (OR 1.65, 95% CI 1.37–1.99), H2 antagonists (OR 1.21, 95% CI 1.18–1.24), proton pump inhibitors (OR 1.41, 95% CI 1.16–1.71), and thyroid hormone (OR 1.29, 95% CI 1.13–1.47). Hormone replacement therapy with estrogen (HRT) was associated with decreased risk of hip fracture (OR 0.80, 95% CI 0.65–0.98). There are several medications associated with sustaining a fragility hip fracture. Medical interventions should be considered for patients on these medications, including information about osteoporosis and fracture prevention.

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Declaration

We, the authors, have no conflict of interest or anything to declare. No funding was received for this study.

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Authors and Affiliations

  1. Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Sharri J. Mortensen, Amin Mohamadi & Ara Nazarian

  2. Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA

    Casey L. Wright

  3. Leni and Peter W. May Department of Orthopaedic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Jimmy J. Chan

  4. Department of Orthopaedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Michael J. Weaver & Arvind von Keudell

  5. Harvard Orthopaedic Trauma Initiative, Harvard Medical School, Boston, MA, USA

    Michael J. Weaver, Arvind von Keudell & Ara Nazarian

  6. Department of Orthopaedic Surgery, Yerevan State Medical University, Yerevan, Armenia

    Ara Nazarian

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Appendix: Search Strategy

Appendix: Search Strategy

MEDLINE (Ovid)

(((exp hip fractures/ OR ((hip OR hips) adj3 fracture*).ab,ti) AND (exp osteoporosis/ OR osteoporo*.ab,ti)) OR ((exp osteoporotic fractures/ OR (osteoporo* adj3 fracture*).ab,ti OR fragility fracture*.ab,ti) AND (exp hip/ OR exp hip joint/ OR hip.ab,ti OR hips.ab,ti))).

AND

exp risk/ OR exp odds ratio/ OR (risk OR odds ratio OR hazard ratio).ab,ti.

Embase (Elsevier)

((('hip fracture'/exp OR ((hip OR hips) NEAR/3 fracture*):ab,ti) AND ('osteoporosis'/exp OR osteoporo*:ab,ti)) OR (('fragility fracture'/exp OR (osteoporo* NEAR/3 fracture*):ab,ti OR (fragility NEXT/1 fracture*):ab,ti) AND ('hip'/exp OR hip:ab,ti OR hips:ab,ti))).

AND

('risk'/exp OR 'odds ratio'/exp OR 'hazard ratio'/exp OR (risk OR 'odds ratio' OR 'hazard ratio'):ab,ti).

Web of Science (Clarivate Analytics)

(TS = ((("hip" OR "hips") NEAR/3 "fracture*") AND "osteoporo*").

OR

TS = ((("osteoporo*" NEAR/3 "fracture*") OR "fragility fracture*") AND ("hip" OR "hips"))).

AND

TS = ("risk" OR "odds ratio" OR "hazard ratio").

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Mortensen, S.J., Mohamadi, A., Wright, C.L. et al. Medications as a Risk Factor for Fragility Hip Fractures: A Systematic Review and Meta-analysis. Calcif Tissue Int 107, 1–9 (2020). https://doi.org/10.1007/s00223-020-00688-1

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