Osteoporosis, Bisphosphonate Use, and Risk of Moderate or Worse Hearing Loss in Women

Sharon G. Curhan MD, ScM; Konstantina Stankovic MD, PhD; Christopher Halpin PhD; Molin Wang PhD; Roland D. Eavey MD, SM; Julie M. Paik MD, ScD; Gary C. Curhan MD, ScD


J Am Geriatr Soc. 2021;69(11):3103-3113. 

In This Article

Abstract and Introduction


Background: Osteoporosis and low bone density (LBD) may be associated with higher risk of hearing loss, but findings are inconsistent and longitudinal data are scarce. Bisphosphonates may influence risk, but the relation has not been studied in humans. We longitudinally investigated associations of osteoporosis and LBD, bisphosphonate use, vertebral fracture (VF), hip fracture (HF), and risk of self-reported moderate or worse hearing loss.

Design: Longitudinal cohort study.

Setting: The Nurses' Health Study (NHS) (1982–2016) and Nurses' Health Study II (NHS II) (1995–2017).

Participants: Participants included 60,821 NHS women, aged 36–61 years at baseline, and 83,078 NHS II women, aged 31–48 years at baseline (total n = 143,899).

Measurements: Information on osteoporosis, LBD, bisphosphonate use, VF, HF, and hearing status was obtained from validated biennial questionnaires. In a subcohort (n = 3749), objective hearing thresholds were obtained by audiometry. Multivariable-adjusted Cox proportional hazards models were used to examine independent associations between osteoporosis (NHS), osteoporosis/LBD (NHS II), and risk of hearing loss.

Results: The multivariable-adjusted relative risk (MVRR, 95% confidence interval) of moderate or worse hearing loss was higher among women with osteoporosis or LBD in both cohorts. In NHS, compared with women without osteoporosis, the MVRR was 1.14 (1.09, 1.19) among women with osteoporosis; in NHS II, the MVRR was 1.30 (1.21, 1.40) among women with osteoporosis/LBD. The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates. VF was associated with higher risk (NHS: 1.31 [1.16, 1.49]; NHS II: 1.39 [1.13, 1.71]), but HF was not (NHS: 1.00 [0.86, 1.16];NHS II: 1.15 [0.75,1.74]). Among participants with audiometric measurements, compared with women without osteoporosis/LBD, the mean multivariable-adjusted hearing thresholds were higher (i.e., worse) among those with osteoporosis/LBD who used bisphosphonates.

Conclusion: Osteoporosis and LBD may be important contributors to aging-related hearing loss. Among women with osteoporosis, the risk of hearing loss was not influenced by bisphosphonate use.


Hearing loss is the third most common chronic condition in the United States and can cause considerable disability.[1] Individuals with hearing loss are more likely to have impaired activities of daily living,[2] reduced quality of life,[2] and higher risk of depression[3] and cognitive decline.[4] The Global Burden Disease Study 2013 reported an estimated 1.23 billion individuals have some form of hearing impairment, accounting for 36.5 years lost to disability globally. Furthermore, over 400 million had hearing loss that was moderate or worse in severity, the vast majority of which was classified as age-related hearing loss.[5] Hearing damage is often irreversible, thus identifying potentially modifiable risk factors that may contribute to hearing loss is a pressing public health goal.

Osteoporosis is associated with reduced bone mass and microarchitectural deterioration, leading to compromised bone strength and increased risk of fractures.[6] Vertebral fractures (VFs) are the most common manifestation of osteoporosis;[7] osteoporosis is also strongly related to risk for hip fracture (HF).[8] Animal studies suggest pathways involved in bone homeostasis are also important for cochlear sensorineural integrity and hearing.[9] Some cross-sectional studies in humans found lower bone density and higher prevalence of osteoporosis among individuals with hearing loss, but findings are inconsistent and longitudinal data are lacking.[10,11] Bisphosphonates are the primary therapy for reducing risk of fractures in individuals with osteoporosis and other skeletal conditions characterized by increased osteoclast-mediated bone resorption,[12] and potential benefits of bisphosphonates on hearing have been suggested. A study in noise-exposed mice demonstrated regeneration of cochlear synapses after systemic bisphosphonate administration.[13] In humans with otosclerosis, treatment with a third-generation bisphosphonate was associated with stabilization or improvement of sensorineural hearing loss.[14] The longitudinal association of osteoporosis and hearing loss, and whether bisphosphonate use may influence the risk, is not known. Therefore, we prospectively investigated the association of osteoporosis, bisphosphonate use, and risk of moderate or worse hearing loss in 143,899 participants in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II). We also investigated whether a history of VF or HF, common sites of osteoporotic fractures, were associated with risk of hearing loss.