The Impact of Various Anti-Osteoporosis Drugs on All-Cause Mortality After Hip Fractures: A Nationwide Population Study

Anti-osteoporosis treatment following hip fractures may reduce the overall mortality rate. However, the effects of different drugs on mortality is still unclear. This population-based cohort study aimed to identify the degree of reduced mortality after various anti-osteoporosis regimens following hip fracture surgery. We conducted this cohort study to identify patients with newly diagnosed osteoporosis and hip fractures from 2009 to 2017 using the Taiwan National Health Insurance Research Database (NHIRD). The subsequent use of anti-osteoporosis medication following hip fracture surgery was collected and analyzed. National death registration records were retrieved to determine mortality. A total of 45,226 new cases of osteoporotic hip fracture were identified. Compared with patients who did not receive further treatment, patients who had ever used oral bisphosphonates (alendronate and risedronate, hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.78–0.84), ibandronate (HR 0.76; 95% CI, 0.67–0.86), zoledronic acid (HR 0.70; 95% CI, 0.64–0.76), and denosumab (HR 0.64; 95% CI, 0.60–0.68) showed lower all-cause mortality rates. Patients treated with bisphosphonates had a lower mortality risk than those treated with selective estrogen receptor modulators (HR 0.81; 95% CI, 0.75–0.87). Patients treated with zoledronic acid showed a lower mortality risk than those treated with oral bisphosphonates (HR 0.89; 95% CI, 0.82–0.97). However, patients receiving denosumab and zoledronic acid did not show a significant difference in mortality (HR 0.94; 95% CI, 0.85–1.03). Different anti-osteoporosis treatments for postsurgical patients were associated with different levels of decline in mortality. Generally, longer durations of drug use were associated with lower mortality. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Educational Inequalities in Post‐Hip Fracture Mortality: A NOREPOS Studys

Hip fractures are associated with high excess mortality. Education is an important determinant of health, but little is known about educational inequalities in post‐hip fracture mortality. Our objective was to investigate educational inequalities in post‐hip fracture mortality and to examine whether comorbidity or family composition could explain any association. We conducted a register‐based population study of Norwegians aged 50 years and older from 2002 to 2010. We measured total mortality according to educational attainment in 56,269 hip fracture patients (NORHip) and in the general Norwegian population. Both absolute and relative educational inequalities in mortality in people with and without hip fracture were compared. There was an educational gradient in post‐hip fracture mortality in both sexes. Compared with those with primary education only, the age‐adjusted relative risk (RR) of mortality in hip fracture patients with tertiary education was 0.82 (95% confidence interval [CI] 0.77–0.87) in men and 0.79 (95% CI 0.75–0.84) in women. Additional adjustments for Charlson comorbidity index, marital status, and number of children did not materially change the estimates. Regardless of educational attainment, the 1‐year age‐adjusted mortality was three‐ to fivefold higher in hip fracture patients compared with peers in the general population without fracture. The absolute differences in 1‐year mortality according to educational attainment were considerably larger in hip fracture patients than in the population without hip fracture. Absolute educational inequalities in mortality were higher after hip fracture compared with the general population without hip fracture and were not mediated by comorbidity or family composition. Investigation of other possible mediating factors might help to identify new targets for interventions, based on lower educational attainment, to reduce post‐hip fracture mortality. © 2015 American Society for Bone and Mineral Research.     

Red Cell Distribution Width as an Independent Predictor of Long‐Term Mortality in Hip Fracture Patients: A Prospective Cohort Study

Red blood cell distribution width (RDW) has been found to be a significant prognostic factor of mortality in many cardiovascular diseases. However, a link between RDW at admission with long‐term mortality in the hip fracture population has not been well established. Therefore, we sought to evaluate the long‐term prognostic value of RDW in a well‐defined hip fracture cohort, and to compare the effect of RDW in patients with and without anemia. A prospective cohort study was performed on 1479 hip fracture patients admitted at the General Hospital of Chinese PLA between January 2000 and October 2011 with a follow‐up study over a 2‐year period. A total of 1479 patients were used for the evaluation of 2‐year all‐cause mortality, while 804 patients with more than 4 years of follow‐up were extracted for further evaluation of 4‐year all‐cause mortality. Cox proportional regression was used to evaluate the association between admission RDW and long‐term mortality, adjusting for potential confounding variables. Higher RDW values were strongly associated with increased all‐cause mortality. After adjusting for age, mean corpuscular volume, admission hemoglobin, comorbidities, and complications, RDW had a significant independent association with both 2‐year mortality with a hazard ratio (HR) of 1.183 (95% confidence interval [CI], 1.017 to 1.376) and 4‐year mortality with an HR of 1.244 (95% CI, 1.052 to 1.471). In stratified analysis, the effect of RDW was even more pronounced, with 2‐year mortality HR of 1.341 (95% CI, 1.095 to 1.643) and 4‐year mortality HR of 1.345 (95% CI, 1.071 to 1.688) in non‐anemic patients. In non‐anemic patients, elevated RDW values are significantly associated with increased odds of all‐cause mortality, implying that RDW may be a possible laboratory biomarker for risk stratification in non‐anemic hip fracture patients. Further studies are needed to confirm the current finding in different and larger hip fracture cohorts. © 2015 American Society for Bone and Mineral Research.     

Fruit and Vegetable Intake and Risk of Hip Fracture: A Cohort Study of Swedish Men and Women

Dietary guidelines recommend a daily intake of 5 servings of fruits and vegetables. Whether such intakes are associated with a lower risk of hip fracture is at present unclear. The aim of the present study was to investigate the dose‐response association between habitual fruit and vegetable intake and hip fracture in a cohort study based on 40,644 men from the Cohort of Swedish Men (COSM) and 34,947 women from the Swedish Mammography Cohort (SMC) (total n = 75,591), free from cardiovascular disease and cancer, who answered lifestyle questionnaires in 1997 (age 45 to 83 years). Intake of fruits and vegetables (servings/day) was assessed by food frequency questionnaire and incident hip fractures were retrieved from the Swedish Patient Register (1998 to 2010). The mean follow‐up time was 14.2 years. One‐third of the participants reported an intake of fruits and vegetables of >5 servings/day, one‐third reported >3 to ≤5 servings/day, 28% reported >1 to ≤3 servings/day, and 6% reported ≤1 serving/day. During 1,037,645 person‐years we observed 3644 hip fractures (2266 or 62% in women). The dose‐response association was found to be strongly nonlinear (p < 0.001). Men and women with zero consumption had 88% higher rate of hip fracture compared with those consuming 5 servings/day; adjusted hazard ratio (HR) was 1.88 (95% CI, 1.53 to 2.32). The rate was gradually lower with higher intakes; adjusted HR for 1 versus 5 servings/day was 1.35 (95% CI, 1.21 to 1.58). However, more than 5 servings/day did not confer additionally lower HRs (adjusted HR for 8 versus 5 servings/day was 0.96; 95% CI, 0.90 to 1.03). Similar results were observed when men and women were analyzed separately. We conclude that there is a dose‐response association between fruit and vegetable intake and hip fracture such that an intake below the recommended five servings/day confers higher rates of hip fracture. Intakes above this recommendation do not seem to further lower the risk. © 2014 American Society for Bone and Mineral Research.     

Incidence of Subsequent Hip Fracture and Mortality in Elderly Patients: A Multistate Population-Based Cohort Study in Eastern Spain

Osteoporotic hip fractures in older people may confer an increased risk of subsequent hip fractures and death. The aim of this study was to estimate the cumulative incidence of both recurrent hip fracture and death in the Valencia region. We followed a cohort of 34,491 patients aged ≥65 years who were discharged alive from Valencia Health System hospitals after an osteoporotic hip fracture between 2008 and 2015, until death or end of study (December 31, 2016). Two Bayesian illness-death models were applied to estimate the cumulative incidences of recurrent hip fracture and death by sex, age, and year of discharge. We estimated 1-year cumulative incidences of recurrent hip fracture at 2.5% in women and 2.3% in men, and 8.3% and 6.6%, respectively, at 5 years. Cumulative incidences of total death were 18.3% in women and 28.6% in men at 1 year, and 51.2% and 69.8% at 5 years. One-year probabilities of death after recurrent hip fracture were estimated at 26.8% and 43.8%, respectively, and at 57.3% and 79.2% at 5 years. Our analysis showed an increasing trend in the 1-year cumulative incidence of recurrent hip fracture from 2008 to 2015, but a decreasing trend in 1-year mortality. Male sex and age at discharge were associated with increased risk of death. Women showed higher incidence of subsequent hip fracture than men although they were at the same risk of recurrent hip fracture. Probabilities of death after recurrent hip fracture were higher than those observed in the general population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Chronic Kidney Disease Increases the Risk of Hip Fracture: A Prospective Cohort Study in Korean Adults

This study was conducted to examine the association between renal function and hip fracture. We followed up 352,624 Korean adults, who participated in health examinations during 2009–2010 until 2013. Kidney function was assessed by creatinine-based estimated glomerular filtration rate (eGFR) and albuminuria using urine reagent strip results. The incidence of hip fracture was examined by hospital discharge records. Hazard ratios (HRs) for hip fracture were calculated using Cox proportional hazard models after adjusting for multiple confounders. During a mean follow-up of 4.0 years, 1177 participants suffered a hip fracture. Lower eGFR and more severe albuminuria were associated with a higher risk of hip fracture. The HRs for hip fracture were 1.89 (95% confidence interval [CI] 1.47–2.43) and 3.75 (95% CI 2.30–6.11) among participants with eGFRs of 30 to 44 and 15 to 29 mL/min/1.73m² relative to those with an eGFR ≥60 mL/min/1.73m², respectively. The HRs were 1.30 (95% CI 1.02–1.65) for moderate albuminuria and 1.58 (95% CI 1.07–2.35) for severe albuminuria (p for trend = 0.002). Participants with albuminuria had a higher risk of hip fracture than those without albuminuria, even when they belonged to the same eGFR category (HR = 1.75 versus 3.30 for an eGFR of 30 to 44 mL/min/1.73m²; HR = 2.72 versus 7.84 for an eGFR of 15 to 29 mL/min/1.73m²). The effects of each 10 mL/min/1.73m² decrease in eGFR were stronger with advancing albuminuria severity (p_interaction = 0.016). In conclusion, both low eGFR and albuminuria were risk factors for incident hip fracture in Korean adults. Moreover, these factors exerted a synergistic effect on the risk of hip fracture. © 2020 American Society for Bone and Mineral Research.     

Mortality After Atypical Femoral Fractures: A Cohort Study

Although osteoporotic fracture rates can be reduced by bisphosphonates, prolonged therapy is associated with higher risk of atypical femoral fractures. Ordinary fragility fractures are linked to high mortality rates. We aimed to determine whether atypical femoral fractures also confer excess mortality. Radiographs were reviewed for all patients aged ≥55 years who had experienced a subtrochanteric or femoral shaft fracture in Sweden in 2008 to 2010. The fractures were classified as either atypical or ordinary. Data on medication use, coexisting conditions, and date of death were obtained from national registers. We estimated multivariable‐adjusted relative risks of death after atypical femoral fractures compared with ordinary subtrochanteric or femoral shaft fractures and calculated age‐ and sex‐standardized mortality ratios (SMRs) for atypical and ordinary fractures compared with the population average. During a mean of 4 years of follow‐up, 39 of 172 (23%) patients with an atypical fracture had died compared with 588 of 952 (62%) with an ordinary fracture, corresponding to a relative risk of 0.51 (95% confidence interval [CI] 0.38–0.68). The lower risk was evident in both users and nonusers of bisphosphonates. No patient with atypical fracture died in the first year after fracture. Individuals with an ordinary fracture had a higher mortality risk than the general population (SMR = 1.82; 95% CI 1.69–1.99), but no excess risk was found in patients with atypical fracture (SMR = 0.92; 95% CI 0.65–1.26). We conclude that in contrast to ordinary subtrochanteric and femoral shaft fractures, atypical femoral fractures are not associated with excess mortality. © 2015 American Society for Bone and Mineral Research.     

Increased Mortality in Hip Fracture Patients Living Alone: A NOREPOS Study

Hip fracture is associated with excess mortality, persisting for many years after the fracture. Several factors may affect survival; however, the role of social support has been less studied. Living situation could be an indicator of a person's social support, which predicts mortality in the general population. In this longitudinal cohort study, we considered whether living alone was a risk factor for post-hip fracture mortality compared with living with a partner. Information on hip fractures from all hospitals in Norway from 2002 to 2013 was combined with the 2001 National Population and Housing Census. The association between living situation and mortality during 12.8 years of follow-up in 12,770 men and 22,067 women aged 50 to 79 years at fracture was investigated using flexible parametric survival analysis. We also estimated relative survival of hip fracture patients compared with that of the non-fractured background population in the same living situation (alone or with a partner). Higher mortality after hip fracture was found in both men and women living alone versus with a partner (hazard ratio [HR] men = 1.37, 95% confidence interval [CI] 1.29—1.44; HR women = 1.23, 95% CI 1.18—1.28, adjusting for age, education level, urbanization degree, and number of children). We demonstrated the strongest association in male hip fracture patients aged <60 years (long-term mortality HR = 3.29, 95% CI 2.25—6.49). Compared with the general population, relative survival 8 years after a hip fracture was 43% in men and 61% in women living alone, whereas relative survival in those living with a partner was 51% in men and 67% in women. In conclusion, hip fracture patients who lived alone had higher mortality than those living with a partner and lower survival relative to the general population. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Fruit and Vegetable Intake and Hip Fracture Incidence in Older Men and Women: The CHANCES Project

The role of fruit and vegetable intake in relation to fracture prevention during adulthood and beyond is not adequately understood. We investigated the potential association between fruit and vegetable intake and hip fracture incidence in a large sample of older adults from Europe and the United States. A total of 142,018 individuals (116,509 women) aged ≥60 years, from five cohorts, were followed up prospectively for 1,911,482 person‐years, accumulating 5552 hip fractures. Fruit and vegetable intake was assessed by validated, cohort‐specific, food‐frequency questionnaires (FFQ). Ηip fractures were ascertained through national patient registers or telephone interviews/questionnaires. Adjusted hazard ratios (HRs) derived by Cox proportional hazards regression were estimated for each cohort and subsequently pooled using random effects meta‐analysis. Intake of ≤1 serving/day of fruit and vegetables combined was associated with 39% higher hip fracture risk (pooled adjusted HR, 1.39; 95% confidence interval [CI], 1.20 to 1.58) in comparison with moderate intake (>3 and ≤5 servings/day) (p_{for heterogeneity} = 0.505), whereas higher intakes (>5 servings/day) were not associated with lower risk in comparison with the same reference. Associations were more evident among women. We concluded that a daily intake of 1 or <1 servings of fruits and vegetables was associated with increased hip fracture risk in relation to moderate daily intakes. Older adults with such low fruit and vegetable consumption may benefit from raising their intakes to moderate amounts in order to reduce their hip fracture risk. © 2016 American Society for Bone and Mineral Research.     

The Effect of Fall Biomechanics on Risk for Hip Fracture in Older Adults: A Cohort Study of Video-Captured Falls in Long-Term Care

Over 95% of hip fractures in older adults are caused by falls, yet only 1% to 2% of falls result in hip fracture. Our current understanding of the types of falls that lead to hip fracture is based on reports by the faller or witness. We analyzed videos of real-life falls in long-term care to provide objective evidence on the factors that separate falls that result in hip fracture from falls that do not. Between 2007 and 2018, we video-captured 2377 falls by 646 residents in two long-term care facilities. Hip fracture was documented in 30 falls. We analyzed each video with a structured questionnaire, and used generalized estimating equations (GEEs) to determine relative risk ratios (RRs) for hip fracture associated with various fall characteristics. All hip fractures involved falls from standing height, and pelvis impact with the ground. After excluding falls from lower than standing height, risk for hip fracture was higher for sideways landing configurations (RR = 5.50; 95% CI, 2.36–12.78) than forward or backward, and for falls causing hip impact (3.38; 95% CI, 1.49–7.67). However, hip fracture risk was just as high in falls initially directed sideways as forward (1.14; 95% CI, 0.49–2.67), due to the tendency for rotation during descent. Falling while using a mobility aid was associated with lower fracture risk (0.30; 95% CI, 0.09–1.00). Seventy percent of hip fractures involved impact to the posterolateral aspect of the pelvis. Hip protectors were worn in 73% of falls, and hip fracture risk was lower in falls where hip protectors were worn (0.45; 95% CI, 0.21–0.99). Age and sex were not associated with fracture risk. There was no evidence of spontaneous fractures. In this first study of video-captured falls causing hip fracture, we show that the biomechanics of falls involving hip fracture were different than nonfracture falls for fall height, fall direction, impact locations, and use of hip protectors. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Performance Status Modifies the Association Between Vitamin D Receptor Activator and Mortality or Fracture: A Prospective Cohort Study on the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry

Immobilization osteoporosis is characterized by excess bone resorption. Vitamin D receptor activators (VDRA) might have adverse effects in immobilized patients. The objective of this study was to elucidate the impact of performance status (PS) on the associations between VDRA use and outcomes among hemodialysis patients. This is a prospective cohort study. Adults on hemodialysis in the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry were included. Exposure of interest was the use of VDRA. Outcomes were all-cause mortality and hip fracture. Associations between VDRA use and mortality or hip fractures were examined by Cox and Poisson regression analyses, respectively. Among 208,512 subjects, 128,535 were on VDRA. Poor PS was associated with higher calcium (Ca), lower parathyroid hormone, and higher alkaline phosphatase levels. The association between higher Ca levels and VDRA use was stronger among those with poor PS (p interaction 0.007). Adjusted hazard ratio (HR) (95% confidence interval [CI]) for mortality and incidence rate ratio (IRR) for hip fracture was 1.02 (95% CI, 0.99–1.05) and 0.93 (0.86–1.00) among users of VDRA, respectively. The VDRA use was associated with lower mortality and incidence of hip fractures among subjects with good PS but not among subjects with poor PS (p interaction 0.03 and 0.05). Effect modification by PS was observed for cardiovascular (CV) mortality but not for non-CV mortality. In conclusion, VDRA use was associated with better outcomes only among those with good PS. These results suggest that bone and mineral disorders among hemodialysis patients should be treated differently, depending on their performance status. © 2022 American Society for Bone and Mineral Research (ASBMR).     

Celiac Disease Autoimmunity and Hip Fracture Risk: Findings from a Prospective Cohort Study

The impact of celiac disease autoimmunity on bone health is unclear. We investigated the associations of seropositivity for tissue transglutaminase antibodies (tTGA) and endomysial antibodies (EMA) with incident hip fractures using data from a prospective cohort study, Mini‐Finland Health Survey. Baseline serum samples, taken in 1978–80, were tested for tTGA and EMA. Incident hip fractures up to the year 2011 were ascertained from a national hospitalization register. Associations between seropositivity and hip fractures were modeled using Cox proportional hazards regression adjusted for age, sex, body mass index, vitamin D, gamma‐glutamyl transferase, smoking, and self‐rated health. Our analyses were based on 6919 men and women who had no record of celiac disease or hip fracture before the study baseline. A total of 382 individuals had a hip fracture during a median follow‐up of 30 years. Compared with the tTGA‐negative individuals (n = 6350), tTGA‐positive participants (n = 569; with hip fracture, n = 51) had a higher risk of hip fractures (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.17, 2.14). The findings were similar for another tTGA test (n 200; with hip fracture, n = 26; HR = 2.23, 95% CI 1.49, 3.34). We found no evidence for an association between EMA positivity and hip fracture risk (HR = 0.92, 95% CI 0.34, 2.47; n = 74; with hip fracture, n = 4). In our prospective population‐based study of Finnish adults, seropositivity for tTGA was associated with an increased hip fracture risk. © 2014 American Society for Bone and Mineral Research.     

Protective Association of Milk Intake on the Risk of Hip Fracture: Results from the Framingham Original Cohort

Dairy foods are rich in bone‐beneficial nutrients, yet the role of dairy foods in hip fracture prevention remains controversial. Our objective was to evaluate the association of milk, yogurt, cheese, cream, and milk + yogurt intakes with incident hip fracture in the Framingham Original Cohort. A total of 830 men and women from the Framingham Original Cohort, a prospective cohort study, completed a food‐frequency questionnaire (1988 to 1989) and were followed for hip fracture until 2008. In this population‐based study, Cox‐proportional hazards regression was used to estimate hazard ratios (HR) by categories of energy‐adjusted dairy intake (servings/wk), adjusting for standard confounders and covariates. The exposure was energy‐adjusted intakes of milk, yogurt, cheese, cream, and milk + yogurt (servings/wk). Risk of hip fracture over the follow‐up was the primary outcome; the hypothesis being tested was formulated after data collection. The mean age at baseline was 77 years (SD 4.9, range 68 to 96). Ninety‐seven hip fractures occurred over the mean follow‐up time of 11.6 years (range 0.04 to 21.9 years). The mean ± SD (servings/wk) of dairy intakes at baseline were: milk = 6.0 ± 6.4; yogurt = 0.4 ± 1.3; cheese = 2.6 ± 3.1; and cream = 3.4 ± 5.5. Participants with medium (>1 and <7 servings/wk) or higher (≥7 servings/wk) milk intake tended to have lower hip fracture risk than those with low (≤1 serving/wk) intake (high versus low intake HR 0.58, 95% confidence interval [CI] 0.31–1.06, p = 0.078; medium versus low intake HR 0.61, 95% CI 0.36–1.08, p = 0.071; p trend = 0.178]. There appeared to be a threshold for milk, with 40% lower risk of hip fracture among those with medium/high milk intake compared with those with low intake (p = 0.061). A similar threshold was observed for milk + yogurt intake (p = 0.104). These associations were further attenuated after adjustment for femoral neck bone mineral density. No significant associations were seen for other dairy foods (p range = 0.117 to 0.746). These results suggest that greater intakes of milk and milk + yogurt may lower risk for hip fracture in older adults through mechanisms that are partially, but not entirely, attributable to effects on bone mineral density. © 2014 American Society for Bone and Mineral Research.     

Excess Mortality After Pelvic Fractures Among Older People

The study aimed to estimate excess mortality in patients aged 60 years or older up to 1 year after pelvic fracture compared with a population without pelvic fracture. In this retrospective population‐based observational study, we use routine data from a large health insurance in Germany. For each patient with a first pelvic fracture between 2008 and 2010 (n = 5685 cases, 82% female, mean age 80 ± 9 years), about 34 individuals without pelvic fracture (n = 193,159 controls) were frequency matched by sex, age at index date, and index month. We estimated survival probabilities in the first year after the index date separated for cases (further stratified into inpatient/outpatient treated or minor/major pelvic fractures) and controls using Kaplan‐Meier curves. Additionally, time‐dependent hazard ratios (HRs) measuring excess mortality in 4‐week intervals up to 52 weeks were estimated by fitting Cox regression models including adjustment for relevant confounders. Twenty‐one percent of cases and 11% of controls died within 1 year. HRs (95% confidence intervals) decreased from 3.9 (3.5–4.5) within the first 4 weeks to 1.4 (1.1–1.9) within weeks 49 to 52 after the index date. After full adjustment, HRs lowered substantially (3.0 [2.6–3.4] and 1.0 [0.8–1.4]) but were still significantly increased up to week 32. Adjusted HRs in women were lower than in men: 2.8 (2.4–3.2) and 1.0 (0.7–1.4) versus 3.8 (2.9–5.0) and 1.2 (0.6–2.3). We found a clear excess mortality among older people in the first 8 months after pelvic fracture even after full adjustment. Excess mortality was higher among men in the beginning as well as for inpatient‐treated persons. Absence of excess mortality was noticed for outpatient‐treated persons within the first 3 months. When broken down into site‐specific data, excess mortality was no longer significant for most pelvic fractures classified as minor. The only exception was fracture of pubis within the first 4 weeks. © 2017 American Society for Bone and Mineral Research.     

The Association Between Protein Intake by Source and Osteoporotic Fracture in Older Men: A Prospective Cohort Study

Dietary protein is a potentially modifiable risk factor for fracture. Our objectives were to assess the association of protein intake with incident fracture among older men and whether these associations varied by protein source or by skeletal site. We studied a longitudinal cohort of 5875 men (mean age 73.6 ± 5.9 years) in the Osteoporotic Fractures in Men (MrOS) study. At baseline, protein intake was assessed as percent of total energy intake (TEI) with mean intake from all sources = 16.1%TEI. Incident clinical fractures were confirmed by physician review of medical records. There were 612 major osteoporotic fractures, 806 low‐trauma fractures, 270 hip fractures, 193 spine fractures, and 919 non‐hip non‐spine fractures during 15 years of follow‐up. We used Cox proportional hazards models with age, race, height, clinical site, TEI, physical activity, marital status, osteoporosis, gastrointestinal surgery, smoking, oral corticosteroids use, alcohol consumption, and calcium and vitamin D supplements as covariates to compute hazard ratios (HRs) with 95% confidence intervals (CIs), all expressed per unit (SD = 2.9%TEI) increase. Higher protein intake was associated with a decreased risk of major osteoporotic fracture (HR = 0.92; 95% CI, 0.84 to 1.00) with a similar association found for low‐trauma fracture. The association between protein and fracture varied by protein source; eg, increased dairy protein and non‐dairy animal protein were associated with a decreased risk of hip fracture (HR = 0.80 [95% CI, 0.65 to 0.98] and HR = 0.84 [95% CI, 0.72 to 0.97], respectively), whereas plant‐source protein was not (HR = 0.99 [95% CI, 0.78 to 1.24]). The association between protein and fracture varied by fracture site; total protein was associated with a decreased risk of hip fracture (HR = 0.84 [95% CI, 0.73 to 0.95]), but not clinical spine fracture (HR = 1.06 [95% CI, 0.92 to 1.22]). In conclusion, those with high protein intake (particularly high animal protein intake) as a percentage of TEI have a lower risk of major osteoporotic fracture. © 2016 American Society for Bone and Mineral Research.