Health care providers can empower patients through education.
Osteoporosis is a major health concern characterized by decreased bone strength and bone quality. It also increases risk of osteoporotic fractures, which are associated with reduced quality of life due to greater disability and more frequent hospital admission, as well as increased risk of death.1 Optimal management of osteoporosis requires greater awareness of its risk factors, routine screening, and appropriate utilization of osteoporotic medications that improve bone mineral density (BMD) and reduce the risk of osteoporotic fractures.
Independent of changes in bone mass, aging increases the risk of fractures, with a 20-year increase in age associated with a four-fold increase in fracture risk.7 Menopause predisposes women to osteoporosis due to declining estrogen levels. Although men can also develop osteoporosis, they are less likely to do so than are women because they don’t experience the sudden drop in estrogen experienced by females during menopause.
Other risk factors include inadequate nutrition, lifestyle choices such as cigarette smoking, excessive alcohol use, weight, lack of exercise, and some medications including glucocorticoids, anticonvulsants, proton pump inhibitors, thiazolidinediones, antidepressants, loop diuretics, vitamin A and synthetic retinoids, antiretrovirals, and chemotherapeutic drugs (eg, methotrexate).
Calcium and Vitamin D
The Recommended Dietary Allowance (RDA) for calcium is 1,000 mg per day in adults aged 19 to 50 and men aged 51 to 70. The recommendation increases to 1,200 mg a day for women age 51 and older and for men aged 71 and older.10 Adequate vitamin D is needed to absorb calcium. The RDA for vitamin D is 600 IUs (international units) per day in adults aged 19 to 70. The recommendation increases to 800 IUs a day for adults aged 71 and older.11
Oral bisphosphonates include alendronate, ibandronate, and risedronate, while zoledronic acid is an IV formulation. Alendronate and risedronate are effective in reducing vertebral and hip fractures, while ibandronate has only been shown to reduce the incidence of vertebral fractures.1 Alendronate reduces spine and hip fractures by approximately 50% over three years in patients with a prior vertebral fracture or in patients who have osteoporosis at the hip.13 Alendronate reduces the incidence of vertebral fractures by 48% over three years in individuals without a prior vertebral fracture. Risedronate reduces the frequency of vertebral fractures by 41% to 49% and nonvertebral fractures by 36% over three years.14
Oral bisphosphonates should not be used in patients with esophageal or upper gastrointestinal disorders, those who have an inability to stay upright for at least 30 to 60 minutes after administration, or those with chronic kidney disease (estimated glomerular filtration rate <30–35 mL/min). Oral bisphosphonates are poorly absorbed and must be taken on an empty stomach first thing in the morning with 8 ounces of water for maximal absorption. After administration, the patient should not have food, drinks, or medications for at least 30 minutes (alendronate, risedronate) or 60 minutes (ibandronate).1
IV zoledronic acid is given by infusion once yearly for treatment and once every two years for prevention of osteoporosis. It is contraindicated in patients with a creatinine clearance <35 mL/min or in patients with acute renal impairment.1 Zoledronic acid reduces the frequency of vertebral fractures by 70%, hip fractures by 41%, and nonvertebral fractures by 25% over three years.15
A rare complication of bisphosphonates is a break or crack in the middle of the thighbone. A second rare complication is delayed healing of the jawbone (osteonecrosis).
Denosumab has been shown to be more efficacious than bisphosphonates in increasing BMD among postmenopausal women.16 However, the association is not well established, as a trial examining the risk of any fracture as a secondary outcome found no difference in the fracture risk between denosumab and alendronate within one year of treatment initiation.16 Denosumab reduces the occurrence of vertebral fractures by approximately 68%, hip fractures by about 40%, and nonvertebral fractures by about 20% over three years.17
Similar to bisphosphonates, denosumab can also cause breaks or cracks in the middle of the thighbone and osteonecrosis of the jaw. Persons taking denosumab may need to do so indefinitely, as there could be a high risk of spinal column fractures after stopping the medication.18
In a clinical trial, all women with osteoporosis received daily calcium and vitamin D supplements. The patients were then randomly assigned to receive either abaloparatide or placebo for 18 months. Only 0.6% of women receiving abaloparatide experienced fractures, while 4.2% of women receiving placebo experienced fractures. After 25 months of treatment, fractures occurred in 0.6% of women taking abaloparatide and 4.4% of women taking a placebo.24
Benefits in BMD were also noted. At 18 months, women taking abaloparatide had BMD of the spine increase by 9.2%, BMD of the hip increase by 3.4%, and BMD of the femoral neck (where thigh bone meets the hip bone) increase by 2.9%. After taking placebo for 18 months, BMD of the spine increased by 0.5%, BMD of the hip decreased by 0.1%, and BMD of the femoral neck decreased by 0.4%. After 25 months of treatment, women taking abaloparatide had BMD of the spine increase by 12.8%, BMD of the hip increase by 5.5%, and BMD of the femoral neck increase by 4.5%. After taking placebo for 25 months, BMD of the spine increased by 3.5%, BMD of the hip increased by 1.4%, and BMD of the femoral neck increased by 0.5%.24
Romosozumab is indicated for women with a history of osteoporotic fracture and/or multiple risk factors for fracture, and those who have failed or are intolerant to other osteoporosis therapies.25,26 Careful patient selection is necessary, as romosozumab may increase the risk of heart attack, stroke, and cardiovascular death and should be avoided in patients who have had a heart attack or stroke within the previous year.26 Common side effects of romosozumab include injection site reactions, joint pain, and headache.
The safety and efficacy of romosozumab were demonstrated in two clinical trials involving more than 11,000 women with postmenopausal osteoporosis.26 In the first trial, one year of treatment lowered the risk of a new vertebral fracture by 73%. This benefit was maintained over the second year of the trial when romosozumab was followed by one year of denosumab. In the second trial, one year of treatment with romosozumab followed by one year of alendronate reduced the risk of a new vertebral fracture by 50% compared with two years of alendronate alone. Romosozumab followed by alendronate also reduced nonvertebral fractures compared with alendronate alone.
The Influence of Health Care Professionals
— Mark D. Coggins, PharmD, BCGP, FASCP, is vice president of pharmacy services and medication management for skilled nursing centers operated by Diversicare in nine states and is a past director on the board of the American Society of Consultant Pharmacists. He was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.
2. Cooper C, Campion G, Melton LJ 3rd. Hip fractures in the elderly: a world-wide projection. Osteoporos Int. 1992;2(6):285-289.
3. Melton LJ 3rd, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective: how many women have osteoporosis? J Bone Miner Res. 1992;7(9):1005-1110.
4. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004;35(2):375-382.
5. Oden A, et al. Burden of high fracture probability worldwide: secular increases 2010-2040. Osteoporos Int. 2015;26(9):2243-2248.
6. Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci. 2006;1092:385-396.
7. Hui SL, Slemenda CW, Johnston CC Jr. Age and bone mass as predictors of fracture in a prospective study. J Clin Invest. 1988;81:1804.
8. Larsen ER, Mosekilde L, Foldspang A. Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res. 2004;19(3):370-378.
9. Holick MF, Siris ES, Binkley N, et al. Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90(6):3215-3224.
10. Calcium: fact sheet for health professionals. National Institutes of Health, Office of Dietary Supplements website. https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/. Updated November 17, 2021.
11. Vitamin D: fact sheet for health professionals. National Institutes of Health, Office of Dietary Supplements website. https://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/. Updated August 17, 2021.
12. Black DM, Thompson DE, Bauer DC, et al. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group. J Clin Endocrinol Metab. 2000;85(11):4118-4124.
13. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the fracture intervention trial. JAMA. 1998;280:2077-2082.
14. Reginster J, Minne HW, Sorensen OH, et al. Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int. 2000;11(1):83-91.
15. Lambrinoudaki I, Vlachou S, Galapi F, Papadimitriou D, Papadias K. Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women. Clin Interv Aging. 2008;3(3):445-451.
16. Miller PD, Pannacciulli N, Malouf-Sierra J, et al. Efficacy and safety of denosumab vs. bisphosphonates in postmenopausal women previously treated with oral bisphosphonates. Osteoporos Int. 2020;31(1):181-191.
17. Zaheer S, LeBoff M, Lewiecki EM. Denosumab for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2015;11(3):461-470.
18. Noble JA, McKenna MJ, Crowley RK. Should denosumab treatment for osteoporosis be continued indefinitely? Ther Adv Endocrinol Metab. 2021;12:20420188211010052.
19. Mohamad NV, Soelaiman IN, Chin KY. A concise review of testosterone and bone health. Clin Interv Aging. 2016;11:1317-1324.
20. Tracz MJ, Sideras K, Bolona ER, et al. Testosterone use in men and its effects on bone health: a systematic review and meta-analysis of randomized placebo-controlled trials. NCBI Bookshelf website. https://www.ncbi.nlm.nih.gov/books/NBK72539/. Published 2006.
21. Trovas GP, Lyritis GP, Galanos A, et al. A randomized trial of nasal spray salmon calcitonin in men with idiopathic osteoporosis: effects on bone mineral density and bone markers. J Bone Miner Res. 2002;17:521-527.
22. Mehta NM, Malootian A, Gilligan JP. Calcitonin for osteoporosis and bone pain. Curr Pharm Des. 2003;9(32):2659-2676.
23. Tymlos (abaloparatide) injection website. https://www.tymloshcp.com/
24. Radius Health, Inc. Highlights of prescribing information: TYMLOS (abaloparatide) injection, for subcutaneous use. https://radiuspharm.com/wp-content/uploads/tymlos/tymlos-prescribing-information.pdf. Updated December 2021.
25. Paik J, Scott LJ. Romosozumab: a review in postmenopausal osteoporosis. Drugs Aging. 2020;37(11):845-855.
26. FDA approves new treatment for osteoporosis in postmenopausal women at high risk of fracture. U.S. Food & Drug Administration website. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-osteoporosis-postmenopausal-women-high-risk-fracture. Published April 9, 2019.
27. Sujic R, Gignac MA, Cockerill R. A review of patient-centered post-fracture interventions in the context of theories of health behavior change. Osteoporos Int. 2011;22:2213-2224.
28. Besser SJ, Anderson JE, Weinman J. How do osteoporosis patients perceive their illness and treatment? Implications for clinical practice. Arch Osteoporos. 2012;7:115-124.