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

Mortensen, Sharri J.; Mohamadi, Amin; Wright, Casey L.; Chan, Jimmy J.; Weaver, Michael J.; Keudell, Arvind von; Nazarian, Ara

doi:10.1007/s00223-020-00688-1

Cited by 38 publications

(52 citation statements)

References 73 publications

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“…Therefore, these drugs are commonly prescribed for patients with major neurocognitive disorders. Previous studies have suggested that the use of cholinesterase inhibitors 3 4 and antipsychotic drugs 10 11 12 13 14 15 16 17 18 19 20 21 22 could be associated with the risk of falls and fractures because of some of the side effects, such as hypotension, syncope, and extrapyramidal symptoms. Confounding by indication should be considered, however, because patients might already have been at high risk of falls and fractures before the treatment started.…”

Section: Discussionmentioning

confidence: 99%

“… 7 Because of the potential adverse effects of antipsychotic drugs, including orthostatic hypotension, sedation, blurred vision, and extrapyramidal symptoms, the United States Food and Drug Administration has suggested that a complete assessment of the risk of falls should be undertaken before the start of treatment. 8 Beers criteria 9 and other studies 10 11 12 13 14 15 16 17 18 19 20 21 22 have also suggested that antipsychotic drugs might be associated with the risk of falls and fractures.…”

Section: Introductionmentioning

confidence: 99%

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Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series

Wang

Man²,

Chang

et al. 2021

BMJ

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Objective To evaluate the association between the use of antipsychotic drugs and cholinesterase inhibitors and the risk of falls and fractures in elderly patients with major neurocognitive disorders. Design Self-controlled case series. Setting Taiwan’s National Health Insurance Database. Participants 15 278 adults, aged ≥65, with newly prescribed antipsychotic drugs and cholinesterase inhibitors, who had an incident fall or fracture between 2006 and 2017. Prescription records of cholinesterase inhibitors confirmed the diagnosis of major neurocognitive disorders; all use of cholinesterase inhibitors was reviewed by experts. Main outcome measures Conditional Poisson regression was used to derive incidence rate ratios and 95% confidence intervals for evaluating the risk of falls and fractures for different treatment periods: use of cholinesterase inhibitors alone, antipsychotic drugs alone, and a combination of cholinesterase inhibitors and antipsychotic drugs, compared with the non-treatment period in the same individual. A 14 day pretreatment period was defined before starting the study drugs because of concerns about confounding by indication. Results The incidence of falls and fractures per 100 person years was 8.30 (95% confidence interval 8.14 to 8.46) for the non-treatment period, 52.35 (48.46 to 56.47) for the pretreatment period, and 10.55 (9.98 to 11.14), 10.34 (9.80 to 10.89), and 9.41 (8.98 to 9.86) for use of a combination of cholinesterase inhibitors and antipsychotic drugs, antipsychotic drugs alone, and cholinesterase inhibitors alone, respectively. Compared with the non-treatment period, the highest risk of falls and fractures was during the pretreatment period (adjusted incidence rate ratio 6.17, 95% confidence interval 5.69 to 6.69), followed by treatment with the combination of cholinesterase inhibitors and antipsychotic drugs (1.35, 1.26 to 1.45), antipsychotic drugs alone (1.33, 1.24 to 1.43), and cholinesterase inhibitors alone (1.17, 1.10 to 1.24). Conclusions The incidence of falls and fractures was high in the pretreatment period, suggesting that factors other than the study drugs, such as underlying diseases, should be taken into consideration when evaluating the association between the risk of falls and fractures and use of cholinesterase inhibitors and antipsychotic drugs. The treatment periods were also associated with a higher risk of falls and fractures compared with the non-treatment period, although the magnitude was much lower than during the pretreatment period. Strategies for prevention and close monitoring of the risk of falls are still necessary until patients regain a more stable physical and mental state.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series

Wang

Man²,

Chang

et al. 2021

BMJ

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“…OP increases fracture risk and requires treatment to prevent subsequent comorbidities and mortality after fracture [ 19 , 22 , 25 , 26 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ]. Knee OA leads to an increased risk of fall, which therefore increases fracture risk and required treatment [ 77 , 78 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

Cheng

Chang

et al. 2021

Biomedicines

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Osteoarthritis (OA) and osteoporosis (OP) are common among older women, especially postmenopausal women. Glucosamine (GlcN) is a common medication for OA, but it may induce insulin resistance and β-cell dysfunction, especially if ovarian hormones are lacking. Raloxifene (RLX) is a selective estrogen receptor modulator and also an OP drug. Previously, we found that estrogen could improve GlcN-induced insulin resistance in ovariectomized (OVX) rats. Here, we further hypothesized that RLX, similarly to estrogen, can ameliorate GlcN-induced insulin resistance in OVX rats. We used GlcN to induce insulin resistance in OVX rats as a model for evaluating the protective effects of RLX in vivo. We used a pancreatic β-cell line, MIN-6, to study the mechanisms underlying the effect of RLX in GlcN-induced β-cell dysfunction in vitro. Increases in fasting plasma glucose, insulin, and homeostasis model assessments of insulin resistance in OVX Sprague Dawley rats treated with GlcN were reversed by RLX treatment (n = 8 in each group). Skeletal muscle GLUT-4 increased, liver PEPCK decreased, pancreatic islet hypertrophy, and β-cell apoptosis in OVX rats treated with GlcN was ameliorated by RLX. The negative effects of GlcN on insulin secretion and cell viability in MIN-6 cells were related to the upregulation of reticulum (ER) stress-associated proteins (C/EBP homologous protein, phospho-extracellular signal-regulated kinase, phospho-c-JunN-terminal kinase), the expression of which was reduced by RLX. Pretreatment with estrogen receptor antagonists reversed the protective effects of RLX. GlcN can induce insulin resistance, β-cell dysfunction, and apoptosis in OVX rats and increase ER stress-related proteins in β-cells, whereas RLX can reverse these adverse effects. The effects of RLX act mainly through estrogen receptor α; therefore, RLX may be a candidate drug for postmenopausal women with OA and OP.

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“…Several meta-analyses of observational studies have reported a decreased risk of fractures with the use of thiazide diuretics, mainly involving hip fractures [234][235][236][237][238]. However, not all published meta-analyses on this topic report the same results.…”

Section: Thiazide Diureticsmentioning

confidence: 99%

The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density

Burgh

Keyser

Zillikens

et al. 2021

Drugs

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

Cited by 38 publications

References 73 publications

Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series

Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density

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