Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women

Key Points Question Are plant-based diets associated with risk of hip fractures in postmenopausal women? Findings In this cohort study that included 70 285 postmenopausal women in the US, long-term adherence to a plant-based diet was not associated with the risk of hip fracture. However, comparing lowest to highest quintiles of Plant-Based Diet Index scores, the most recent intake of a healthy plant-based diet was associated with 21% lower risk of fracture, whereas the most recent intake of an unhealthy plant-based diet was associated with 28% higher risk of fracture. Meaning Findings of this cohort study suggest that following a plant-based diet over time appears safe regarding the risk of hip fracture.


Introduction
Bone fractures are a public health issue 1 among older adults because bone mass decreases with age, especially in postmenopausal women.Worldwide, 1 in 3 women older than 50 years will experience a fragility fracture, 2 which is a leading cause of long-term morbidity. 3equate nutrient intake plays an essential role in bone mineralization.Some nutrients, such as calcium, vitamin D, or vitamin K, have shown an association with reduced bone loss. 4,5Although a systematic review of clinical trials and observational studies showed that dietary calcium intake or dairy consumption was not associated with risk of fractures, [5][6][7][8][9][10] a recent study found that high dietary calcium intake in the context of a Mediterranean-style diet was associated with lower risk of fractures. 113][14] In fact, the combined, very high intake of vitamins B 6 and B 12 has been associated with increased risk of hip fractures in postmenopausal women. 15ant-based diets, characterized by higher consumption of plant foods and lower or no intake of animal foods, have raised concerns about their potential harmful effect on bone health related to the shortfalls of a vegetarian diet. 16A systematic review found that vegetarians, but particularly vegans (defined as those with no consumption of any source of animal food), had higher risk of fractures and lower bone mineral density compared with omnivores. 14Likewise, a previous study in the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Oxford cohort found that compared with meat eaters, fish eaters and vegetarians had higher risk of hip fractures. 17However, none of those studies assessed the quality of the plant-based diets, which is important because not all plant-based diets are healthy. 169][20][21][22] However, evidence is limited about the association between the Plant-Based Diet Index (PDI) and risk of fractures.Therefore, our aim was to study the association between plant-based diet quality and risk of hip fracture among postmenopausal women in the Nurses' Health Study (NHS).Of note is that the PDI does not necessarily correspond to a vegan or vegetarian diet.Instead, the PDI is a composite score assessing the quality of plant-derived foods, and it does not exclude the consumption of animal foods but rather scores them reversed.

Study Population
The NHS is a prospective cohort study that started in 1976 and included 121 700 female registered nurses in the United States aged 30 to 55 years. 23Every 2 years, participants provided information about medical history and health-related information.In addition, every 4 years, a food frequency questionnaire (FFQ) was sent to obtain dietary information.Follow-up rates exceed 90%.For the present analysis, only White postmenopausal women were included at baseline (1984).Otherwise, women entered the questionnaire cycle when they reached menopause, including surgical menopause.Women with different races and ethnicities were excluded because their numbers were very low.We excluded participants at entry with cancer (as the medical treatment may affect bone mineral density), with a previously reported hip fracture or osteoporosis (because participants at higher risk of fracture may change their diet), or with missing diet information (eFigure in

Assessment of PDIs
Dietary data were collected with a self-administered semiquantitative FFQ 24 every 4 years between 1984 and 2010.Participants were asked how often on average during the previous 12 months they had consumed each food of a standard portion size.Reliability and validity of the FFQ have been reported elsewhere. 25o types of a PDIs were computed to consider the quality of the foods included, a healthful PDI (hPDI) and an unhealthful PDI (uPDI).Details about food groups and scoring criteria for both indices have been previously reported. 26,27In brief, all food items were classified into 18 food groups based on nutrients and culinary similarities, and these groups were classified into 3 larger categories of healthy plant foods, less healthy plant foods, and animal foods.The 18 food groups were ranked into quintiles, and each quintile was given a positive or reversed score, with a range from 1 to 5 (eTable 1 in Supplement 1).For the hPDI, the healthy plant food groups were given positive scores, whereas the less healthy plant food and animal food groups were given a reversed score.For the uPDI, positive scores were given to less healthy plant food groups, and reversed scores to healthy plant food groups and animal food groups.The quintile scores of the 18 food groups were summed, so the theoretical range for both the hPDI and the uPDI was from 18 to 90 (highest adherence).

Assessment of Hip Fractures
Participants in the study reported any hip fractures they experienced, including the month and year that they occurred, on biennial questionnaires.Participants also provided details about the circumstances surrounding the fracture, which were used to determine the level of trauma.Fractures caused by high-impact trauma, such as motor vehicle crashes, horseback riding, skiing, and similar activities, were not included.A validation study using medical records conducted within the NHS confirmed every reported fracture in all 30 cases examined. 28Finally, hip fractures were identified from death records as well.

Assessment of Other Lifestyle Characteristics
Biannually, we collected information on age, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking status, and use of thiazide diuretics, furosemide-like diuretics, anti-inflammatory steroids, and postmenopausal hormone treatment.Participants reported use of brand-specific multivitamins; use of supplementation with calcium, vitamin D, and retinol; and receipt of a diagnosis of diabetes.Leisure-time physical activity was assessed with up to 10 activities 29 from which metabolic equivalent of task hours per week were calculated.

Statistical Analysis
Participants were followed up from the date of the questionnaire cycle that they first reported being in menopause (FFQ in 1984 as the first diet assessment) until the date of first hip fracture, death from hip fracture, last questionnaire response, or the end of follow-up in 2014, whichever came first.For the primary analysis, to capture the long-term diet, we used a cumulative mean of the hPDI and uPDI scores (ie, the mean diet across points of data collection).In a secondary analysis, to assess the recent diet, we used dietary information from the FFQ prior to the hip fracture or the end of follow-up, whichever was earlier.To assess the baseline diet, we used dietary information from the FFQ when the participant first reported being postmenopausal.
We used Cox proportional hazards regression models (with time-varying covariates when the exposure was the long-term dietary indices using the updated information for covariates in each cycle [ie, BMI, physical activity, energy intake, and alcohol consumption] and baseline covariates when the exposure was the baseline diet) to compute the hazard ratios (HRs) and 95% CIs of hip fracture according to quintiles of the hPDI and uPDI, with the lowest quintile being the reference group.Linear trends were evaluated using quintiles of the indices as a continuous variable.
Additionally, we estimated the risk of hip fracture per 10-unit increase in the hPDI and uPDI.We sequentially adjusted for covariates to assess their association with the HR.In model for age and energy intake.Model 2 additionally adjusted for BMI and height (in centimeters).In model 3, we further adjusted for physical activity, smoking, alcohol intake, and history of diabetes.In our final model (model 4), we adjusted for medication and supplement use that can affect bone mineral density, including the use of thiazides, furosemide-like diuretics, oral anti-inflammatory steroids, and multivitamins, postmenopausal hormone treatment, and supplemental intakes of calcium, retinol, and vitamin D.
In secondary and sensitivity analyses, we first assessed the associations between individually modified PDIs and risk of hip fracture, including an hPDI with a positive score for yogurt, fish, and poultry.We then estimated the association of specific healthy and less healthy plant foods and animal foods with the risk of hip fractures.We next evaluated diet indices reported at different latencies (2, 6, and 10 years) before a hip fracture occurrence to account for potential bias resulting from changes in diet because of signs of bone demineralization or osteoporosis.We also conducted stratified analyses to examine whether any association between the PDI and hip fracture differed by age, BMI, or physical activity; the likelihood ratio test comparing regression models with vs without an interaction term was used to assess the interaction.We addressed residual confounding using the E-value for the null hypothesis 30 Analyses were performed using SAS software for UNIX, version 9.4 (SAS Institute Inc).A 2-sided P < .05 was considered statistically significant.Data were analyzed from January 1 to July 31, 2023.

Results
Of 70 285 participants included in the present study, we ascertained 2038 cases of hip fractures in the NHS during follow-up up to 30 years.The age-adjusted baseline characteristics of the participants according to quintiles of the hPDI and uPDI are presented in Table 1.Overall, at baseline, the mean (SD) age of participants was 54.92 (4.48) years, and 100% were White women.The mean (SD) hPDI was 54.33 (7.33) points, and it was 54.38 (7.70) points for the uPDI.The mean (SD) energy consumption was 1743.65 (521.07)kcal, and the mean (SD) BMI was 25.69 (4.85).Compared with participants with lower hPDI scores, individuals with higher hPDI scores were leaner, more physically active, less likely to be smokers, more likely to use vitamin and calcium supplements, had higher intakes of dietary calcium and healthy plant foods, and had lower intake of less healthy plant foods.
Conversely, those with higher scores in the uPDI were less physically active, more likely to smoke, had lower calcium and alcohol intake, were less likely to use vitamin supplements, had higher consumption of less healthy plant foods, and had lower consumption of healthy plant foods.
Compared with individuals with the least adherence to the hPDI and uPDI, those with the highest adherence to the hPDI and uPDI had lower energy intake and lower vitamin D supplemental intake.
In sensitivity analyses, when we assessed long-term adherence to modified healthy plant-based diets, we did not document any associations between hPDI scores and hip fracture risk (eTable 2 in Supplement 1).Likewise, individual servings of food groups in the hPDI and uPDI were not associated with hip fracture risk (eTable 3 in Supplement 1).Latency analyses did not document any associations of hPDI and uPDI with hip fracture risk (eTable 4 in Supplement 1).We found no significant Finally, assuming a reasonable protective risk factor of 0.90, for the hPDI, we obtained an E-value of 1.38, which describes the magnitude of the association an unmeasured confounder would need to have with the hPDI and risk of fracture to move the observed relative risk (RR) from 0.97 to 0.90.Likewise, for the uPDI, for an unmeasured confounder to shift the observed RR estimate of 1.02 to an RR of 1.15 (reasonable high-risk factor), an unmeasured confounder that was associated with

Discussion
In this cohort study of postmenopausal women in the US, long-term adherence to a plant-based diet was not associated with risk of hip fracture.We, however, found that the most recent hPDI was associated with 21% lower risk of fracture, whereas the most recent uPDI was associated with 28% higher risk of fracture.In addition, higher baseline scores in the uPDI were associated with higher risk of hip fracture.
Studies using repeated dietary measures to examine the associations between long-term usual diet, the nutritionally relevant exposure, and risk of fractures are scarce.An analysis using data from the NHS and the male-counterpart Health Professionals Follow-Up Study showed that of 3 dietary patterns, namely, the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), and the Alternate Healthy Eating Index-2010 (AHEI-2010), only the AHEI-2010 was marginally associated with lower risk of hip fracture in women but not in men. 33A previous analysis in the same cohorts with repeated measures of diet found no association of a prudent and a Western dietary pattern with risk of fractures. 34By contrast, prospective studies using only 1 baseline measurement of diet have shown that a "healthy dietary pattern," 35,36 a Mediterranean diet alone 31 or in combination with calcium supplementation, 11 or the AHEI-2010 32 was associated with lower risk of fracture, whereas the Dietary Inflammatory Index 37 (DII) was associated with higher risk.However, results from the Women's Health Initiative found that 3-year changes in the DII were not associated with risk of fracture and that only the baseline DII was associated with hip fracture risk among younger White women. 38In our study, using only baseline or current diet information, the uPDI was associated with higher risk of hip fracture, and current hPDI was associated with lower risk.These results could be explained by a relatively short-term effect of these dietary patterns potentially influencing the risk of falls (uPDI) due to deficiencies in energy, protein, and micronutrient intake that affect strength and bone health, thus increasing the risk of fracture.But it is also plausible that reverse causation may account for these associations, as individuals with underlying health conditions that predisposed them to higher fracture risk may have changed their diet.In addition, baseline diet may reflect diet early on, which could be an important predictor of bone mineral density when there was more active bone turnover.Further research should confirm these results and clarify their mechanisms.
While most of the healthy dietary patterns share certain components, such as fruits, vegetables, legumes, and cereals, plant-based diets tend to exclude the animal food groups to varying degrees (ie, excluding meat, fish, eggs, dairy, or all of them).Consequently, some researchers argue that plant-based diets or vegetarian diets may fall short of proteins and other nutrients (calcium, vitamin D, and vitamin B 12 ) and thus may lead to higher risk of fractures.The role of protein intake in fracture prevention remains controversial.Adequate dietary protein intake is essential for bone and muscle synthesis and repair because bone and muscle are interconnected tissues.A recent umbrella review of systematic reviews found possible evidence for reduced hip fracture risk with high vs low protein intake, 39 but it remains unclear whether a dose above the current recommendation or type of protein intake (animal or plant protein) may be associated with the results.Animal-based proteins have high amounts of sulfur-containing amino acids, and some research has suggested that these proteins can augment the acid load in the body and lead to bone loss and increased risk of fracture. 40,41However, in our study, we found a null association with risk of hip fracture for individual food groups.In addition, scoring positively the consumption of yogurt, fish, or poultry in the hPDI  did not change the results.In this regard, the consumption of dairy products and calcium supplementation for the prevention of fractures has been debated in the literature. 42e UK Women's Cohort Study has shown greater risk of hip fracture among vegetarians, but no association was found for pescatarians or occasional meat eaters (<5 servings/week) compared with meat eaters (Ն5 servings/week). 43Vegans in EPIC showed higher risk of fractures 17,44 ; of note, they had lower calcium intake and lower BMI than their nonvegan counterparts, and the fracture risk was higher among people with BMI lower than 22.4.In contrast, in the Adventist Health Study 2, among vegans using supplementation with both vitamin D and calcium, the excess risk of hip fracture disappeared. 45Our study differs from the previous ones because our indices do not completely exclude animal consumption but account for the quality of the plant-based foods, and calcium intake was highest among individuals with the greatest adherence to healthy plant-based diets (1129 mg of calcium per day, close to the Recommended Daily Allowance of 1200 mg).
In our study, both physical activity, an established protective factor for hip fractures, and BMI slightly attenuated the association of hPDI and uPDI with hip fracture.Despite previous evidence that lower BMI is associated with higher risk of fracture, 17,46 our analysis did not show a clear difference between strata.Similarly, the UK Women's Cohort Study did not find clear evidence of BMI modifying associations between diet groups and hip fracture risk, but vegetarians tended to have lower BMI. 47In our study, participants with higher adherence to healthy plant-based diets had lower BMI and higher physical activity.

Strengths and Limitations
Our study has several strengths, including the large sample size and long follow-up, which allowed for a substantial number of hip fractures, and the use of repeated assessment of diet and lifestyles over time, which enabled calculating diet scores at different time points rather than using only baseline data, as in most previous studies.This study has limitations.Data on diet, lifestyle, and hip fracture were self-reported, but the FFQ has been validated against biomarkers and diet records, 24 and a validation study with medical records showed that participants accurately reported incidence of hip fracture. 28Despite controlling for many potential confounders, residual confounding cannot be ruled out.The use of antiosteoporotic medication was not adjusted for because of lack of information.
Finally, our study findings may not be generalizable because we included only postmenopausal White women.

Conclusions
The results of this cohort study indicated that long-term adherence to a plant-based diet was not associated with hip fracture risk.Future research should clarify whether the results for recent dietary intake are associated with the relatively short-term effects of these dietary patterns, reverse causality, or both.

Supplement 1 )
. The NHS protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health.Completion and return of the self-administered questionnaires constituted informed consent.This report follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline for observational studies.JAMA Network Open | Nutrition, Obesity, and Exercise Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women

b
Model 2 includes model 1 plus body mass index and height.c Model 3 includes model 2 plus physical activity, smoking, alcohol, and history of diabetes.dModel 4 includes model 3 plus use of postmenopausal hormones, thiazides, furosemide-like diuretics, anti-inflammatory steroids, and multivitamin supplements and supplemental intakes of calcium, vitamin D, and retinol.

1, we adjusted JAMA Network Open | Nutrition, Obesity, and Exercise Plant
-Based Diets and Risk of Hip Fracture in Postmenopausal Women Downloaded from jamanetwork.comby guest on 03/11/2024

Table 1 .
Age-Adjusted Baseline Characteristics According to Quintiles of Plant-Based Diet Indexes in the Nurses' Health Study a Quintile scores of 18 food groups were summed; thus, the theoretical range for the hPDI and for the uPDI was 18 to 90 (highest adherence).bTotalcalciumintake included supplemental sources.cExcludingfruit juices.JAMA NetworkOpen | Nutrition, Obesity, and Exercise Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women JAMA Network Open.2024;7(2):e241107.doi:10.1001/jamanetworkopen.2024.1107(Reprinted) February 29, 2024 5/11 Downloaded from jamanetwork.comby guest on 03/11/2024 both the uPDI and the risk of fracture by an RR of 1.51-fold each could do so, but a weaker confounder could not.

Table 2 .
Risks of Hip Fracture According to Quintiles of Cumulative Plant-Based Diet Index Scores in Postmenopausal Women in the Nurses' Health Study a Model 1 includes age and energy intake.b Model 2 includes model 1 plus body mass index and height.c Model 3 includes model 2 plus physical activity, smoking, alcohol, and history of diabetes.d Model 4 includes model 3 plus (1) use of postmenopausal hormones, thiazides, furosemide-like diuretics, anti-inflammatory steroids, and multivitamin supplements and (2) supplemental intakes of calcium, vitamin D, and retinol.JAMA Network Open | Nutrition, Obesity, and Exercise Plant-Based Diets and Risk of Hip Fracture in Postmenopausal Women JAMA Network Open.2024;7(2):e241107.doi:10.1001/jamanetworkopen.2024.1107(Reprinted) February 29, 2024 6/11 Downloaded from jamanetwork.comby guest on 03/11/2024

Table 3 .
Risk of Hip Fracture According to Quintiles of Most Recent and Baseline Plant-Based Diet Index Scores in the Nurses' Health Study a Model 1 includes age and energy intake.