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

Disclosures

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

Conclusion

In this large nationwide longitudinal study of women with decades of follow-up, osteoporosis and LBD were associated with increased risk of incident moderate or worse hearing loss. The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates. The risk of hearing loss was higher among women with a history of vertebral fracture, but not of HF. Osteoporosis and LBD may be important contributors to aging-related hearing loss.

1 2 3 4 5

Next Section

Funding information
National Institutes of Health, Grant/Award Numbers: AR075117, DC010811, UM1 CA186107, UO1 CA176726

Acknowledgments
We would like to thank Elaine Coughlin-Gifford for her programming help on this project. We would also like to thank the CHEARS Audiology Assessment Arm Site Directors and study sites whose efforts made this project possible: Albert Einstein College of Medicine (Drs. Laura Tocci, Elizabeth Dinces); Callier Center for Communication Disorders (Dr. Kenneth Pugh); Cleveland Hearing & Speech Center (Drs. Michelle Burnett, Laura Brady, Bridgid Whitford); Columbia University Medical Center (Drs. Jaclyn Spitzer, Jessica Galatioto, Anil Lalwani) Henry Ford Hospital (Drs. Jessica Messer, Virginia Ramachandran, Jaclyn Sommerville); Indiana University at Indianapolis (Dr. Rich Miyamoto); LIJ Hearing and Speech Center (Drs. Andrea Vambutas, Leslie Wexler); Massachusetts Eye and Ear Infirmary (Dr. Chris Halpin); Southern New England Ear Nose and Throat (Dr. Ken Yanagisawa); Phelps Memorial Hospital Center (Drs. Judith Christopher, Jessica LaCorte); San Diego Hearing Center (Dr. Blanche Blackington); St. Louis University Medical Center (Dr. David Harris); Stanford Hospital and Clinics (Drs. Gerald Popelka, Matthew Fitzgerald); University of California, Irvine (Dr. Alicia Tratkman); University of Cincinnati (Dr. Stephanie Lockhart); University of Michigan (Drs. Bruce Edwards, Paul Kileny); University of Pennsylvania (Drs. Jennifer Rotz, Michael Ruckenstein); University of Pittsburgh Medical Center (Drs. Catherine Palmer, Lori Zitelli); University of Rochester (Dr. Mark Orlando); Yale University (Dr. Eli Michaelides).

Sponsor's Role
This research was supported by grants DC010811, AR075117, UM1 CA186107, and UO1 CA176726 from the National Institutes of Health.

Table 1. Age-standardized baseline characteristics of women in the Nurses' Health Study (1982) and Nurses' Health Study II (1995), according to osteoporosis or low bone density (LBD)
Characteristic	Nurses' Health Study		Nurses' Health Study II
Characteristic	No osteoporosis n = 57,472	Osteoporosis n = 534	No osteoporosis or LBD n = 81,078	Osteoporosis or LBD n = 1619
Age, years^a (baseline)	46.0 (6.5)	52.6 (5.7)	40.2 (4.6)	43.2 (4.0)
Age, years^a (end of follow-up)	79.1 (6.1)	85.8 (5.9)	62.0 (4.6)	65.0 (4.0)
Mean follow-up, years^a	25.3	21.5	17.9	16.9
Race, white, %	94.5	95.7	94.1	95.0
Body mass index, kg/m²	24.2 (4.2)	24.4 (3.8)	25.7 (5.8)	23.9 (5.2)
Waist circumference, cm^b	77.3 (10.5)	79.4 (9.4)	78 (12.6)	74.4 (11)
Physical activity, METs/week^c	14.6 (21.1)	16 (19.8)	20.8 (26.8)	23 (30.2)
Smoking
Never, %	46.9	41.6	65.9	64.3
Past, %	30.5	32.3	23.8	22.9
Current, %	22.4	26.0	9.9	12.2
Hypertension, %	14.0	23.8	9.2	11.9
Diabetes mellitus, type II, %	1.3	3.8	5.1	7.1
Regular^d ibuprofen use, %	15.1	24.9	23.6	31.2
Regular^d acetaminophen use, %	12.0	18.6	13.0	19.0
Thiazide use, %	9.2	15.1	1.9	3.2
DASH dietary score	23.7 (4.6)	24.5 (4.7)	23.7 (4.9)	23.6 (5.0)
Alcohol intake, g %	6.0 (9.7)	5.3 (8.3)	3.5 (6.6)	3.2 (6.4)
Postmenopausal, %	27.5	49.8	6.6	16.4
Oral hormone therapy use
Never user, %	82.6	50.1	94.0	85.3
<5 years, %	6.3	22.2	2.7	6.2
≥5 years, %	3.6	11.5	1.2	3.8

Note: Values are means (SD) for continuous variables, percentages for categorical variables, and are standardized to the age distribution of the study population. Values of polytomous variables may not sum to 100% due to rounding.
^aValue is not age-adjusted.
^bWaist circumference assessed in 1986 (NHS) and 1993 (NHS II).
^cMetabolic equivalents from recreational and leisure-time activities.
^dRegular analgesic use defined as 2 or more days per week.

Table 2. Osteoporosis and risk of moderate or worse hearing loss among women in the Nurses' Health Study (1982–2016) and Nurses' Health Study II (1995–2017)
	# Cases	Person-years	Age-adjusted RR (95% CI)	MV-adjusted RR^a (95% CI)
NHS
Osteoporosis
No	9194	1,317,265	1.00 (ref)	1.00 (ref)
Yes	3266	192,446	1.15 (1.11, 1.20)	1.14 (1.09, 1.19)
NHS II
Osteoporosis/LBD
No	3389	1,248,902	1.00 (ref)	1.00 (ref)
Yes	1176	219,273	1.29 (1.20, 1.38)	1.30 (1.21, 1.40)

Abbreviations: LBD, low bone density; NHS, Nurses' Health Study; NHS II, Nurses' Health Study II; RR, relative risk.
^aMV-adjusted RR: multivariable-adjusted relative risk adjusted for age, race/ethnicity, body mass index, waist circumference, physical activity, DASH diet score, alcohol intake, thiazide use, history of hypertension, history of diabetes mellitus, type II, smoking, ibuprofen use, acetaminophen use, menopausal status, and oral hormone therapy use.

Table 3. Osteoporosis, bisphosphonate use, and risk of moderate or worse hearing loss in the Nurses' Health Study (1998–2016) and Nurses' Health Study II (1995–2017)
	# Cases	Person-years	Age-adjusted RR (95% CI)	MV-adjusted RR^a (95% CI)
NHS I
Osteoporosis
No	5286	420,028	1.00 (ref)	1.00 (ref)
Yes, no bisphosphonate use	1880	103,332	1.15 (1.09, 1.21)	1.13 (1.07, 1.20)
Yes, bisphosphonate use	928	46,961	1.13 (1.05, 1.21)	1.14 (1.06, 1.22)
NHS II
Osteoporosis/LBD
No	3389	1,248,902	1.00 (ref)	1.00 (ref)
Yes, no bisphosphonate use	736	120,278	1.26 (1.15, 1.38)	1.28 (1.17, 1.40)
Yes, bisphosphonate use	116	17,931	1.40 (1.16, 1.69)	1.40 (1.15, 1.70)

Table 4. Hip and vertebral fracture and risk of moderate or worse hearing loss among women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II)
	# Cases	Person-years	Age-adjusted RR (95% CI)	MV-adjusted RR^a (95% CI)
Hip fracture^b
NHS I
No	8383	609,948	1.00 (ref)	1.00 (ref)
Yes	175	11,138	1.00 (0.86, 1.16)	1.00 (0.86, 1.16)
NHS II
No	4542	1,463,459	1.00 (ref)	1.00 (ref)
Yes	22	4641	1.21 (0.80, 1.85)	1.15 (0.75, 1.74)
Vertebral fracture^c
NHS I
No	5910	412,690	1.00 (ref)	1.00 (ref)
Yes	266	12,571	1.35 (1.20, 1.53)	1.31 (1.16, 1.49)
NHS II
No	4473	1,452,871	1.00 (ref)	1.00 (ref)
Yes	92	15,304	1.53 (1.24, 1.88)	1.39 (1.13, 1.71)

Abbreviations: NHS, Nurses' Health Study; NHS II: Nurses' Health Study II; RR, relative risk.
^aMV-adjusted RR: multivariable-adjusted relative risk adjusted for age, race/ethnicity, body mass index, waist circumference, physical activity, DASH diet score, alcohol intake, thiazide use, history of hypertension, history of diabetes mellitus, type II, smoking, ibuprofen use, acetaminophen use, menopausal status, and oral hormone therapy use.
^bNHS I analysis conducted from 1982 to 2016; NHS II analysis conducted from 1995 to 2017.
^cNHS I analysis conducted from 2002 to 2016; NHS II analysis conducted from 1995 to 2017. VF in NHS confirmed by medical records.

Authors and Disclosures

Sharon G. Curhan MD, ScM^1,2, Konstantina Stankovic MD, PhD^2,3, Christopher Halpin PhD⁴, Molin Wang PhD^1,5,6, Roland D. Eavey MD, SM⁷, Julie M. Paik MD, ScD^1,2,8,9 and Gary C. Curhan MD, ScD^1,2,6,8

¹Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
²Harvard Medical School, Boston, Massachusetts, USA
³Department of Otolaryngology—Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts, USA
⁴Department of Otolaryngology, Massachusetts General Hospital, Boston, Massachusetts, USA
⁵Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA
⁶Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
⁷Vanderbilt Bill Wilkerson Center for Otolaryngology and Communication Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
⁸Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
⁹Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts, USA

Correspondence
Sharon G. Curhan, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02114, USA. Email: scurhan@bwh.harvard.edu

Conflict of Interest
Dr. S. Curhan serves as a consultant to Decibel Therapeutics. Dr. G. Curhan serves as a consultant to Decibel Therapeutics, AstraZeneca, Shire, Allena Pharmaceuticals, RenalGuard, OrfanBiotech, OM1, and Merck. He receives royalties from UpToDate for being an author and Section Editor. The other authors declare no conflicts of interest.

Author Contributions
Dr. S. Curhan led this investigation. Dr. S. Curhan formulated the study question and design, contributed to directing its implementation, performed the statistical analyses, contributed to the acquisition of the data, conducted the analysis and interpretation of the data, conducted the literature review, and wrote the first draft of the manuscript. Dr. Stankovic contributed to the formulation of the study question and the interpretation of the data. Dr. Halpin contributed to the study design and data acquisition. Dr. Wang contributed to the data acquisition and analysis. Dr. Eavey contributed to the study conception and design. Dr. Paik contributed to the formulation of the study question and the analysis and interpretation of the data. Dr. G. Curhan contributed to the study conception and design, supervision of its implementation, data acquisition and analysis, and interpretation of the results. All the authors contributed to the critical revision of the manuscript, approved the final version, and made the decision to submit the manuscript for publication.