Osteoporosis in women

At least one in three women will suffer an osteoporosis fracture in their lifetime,1 a statistic underscoring the ubiquitous nature of this health concern. Notably, hip fractures, a common outcome, are associated with a significant increase in morbidity and mortality. Almost one out of four people who suffer a hip fracture will die of any cause within one year following the fracture.2 The subsequent fear of recurring falls initiates a cascade of consequences including reduced movement, diminished strength and impaired mobility. This compounding effect amplifies the likelihood of future falls necessitating intervention to disrupt this cycle and mitigate fracture risks. Osteoporosis, characterized by reduced bone mass and compromised bone quality lies at the crux of this challenge, serving as a precursor to fractures. This article aims to empower pharmacists to adopt a comprehensive approach to managing primary osteoporosis, acknowledging the concurrent metabolic changes in this life stage. This approach emphasizes the cultivation of a holistic care plan.PathophysiologyBone is living tissue that is strengthened and hardened by calcium and phosphorus. Bone health is important at every stage of life, but especially during adolescence when 50% of bone mass is formed.3 Most people reach their peak bone mass around age 20–30.4 Bone strengthening behaviours (physical activity, nutrition and lifestyle considerations) are important throughout life, beginning in childhood, in order to optimize bone health and reduce the risk of developing osteoporosis later in life.Bone demineralization exceeds bone mineralization as early as age 25.5 Many studies recognize that using combined oral contraceptives in women under the age of 25 can interfere with bone mineralization.6 Pills containing 30–35 µg of ethinyl estradiol (EE) should be prescribed preferentially in women under 25 years old seeking oral contraceptives because EE doses below 30 µg may be associated with poorer bone mineralization in youth, which can impact their bone health later in life.7 Rates of bone loss are highest during menopause, with an approximate loss of 2%–3% per year. By the age of 80, a woman has lost approximately 30% of her peak bone mass.8Risk factors for low bone mineral density (BMD) include advanced age, genetics, smoking, history of fracture, inflammatory illnesses, malabsorption diseases, endocrinopathies and long-term use of certain medications (e.g., anticonvulsants, glucocorticoids, aromatase inhibitors, immunosuppressives).8DiagnosisA staggering 80% of people who have suffered at least one osteoporotic fracture are neither identified nor treated for osteoporosis.9 This statistic underscores the importance of assessing risk factors and screening where appropriate.10Osteoporosis is defined by a T-score of ≤ 2.5 standard deviations below peak bone mass (i.e., a value of ≤ -2.5). A diagnosis can also be made in patients > 50 years of age if they sustained a low-trauma hip, vertebral, humerus or pelvic fracture after the age of 40 years. An absolute fracture risk of ≥ 20% over the next 10 years, determined by using the Fracture Risk Assessment Tool (FRAX, see Box 1) or the Canadian Association of Radiologists Osteoporosis Canada (CAROC) tool, would also result in an osteoporosis diagnosis.10With regards to the fracture assessment tools CAROC and FRAX, FRAX takes into account additional risk factors such as body mass index (BMI), medical conditions resulting in secondary osteoporosis, current smoking, alcohol intake and parental hip fracture; it is the preferred tool recommended in the Osteoporosis Canada 2023 guidelines.10 The FRAX/CAROC clinical tools have not been validated in transgender and non-gender conforming people.10BMD testing guidelinesPharmacists should ensure that patients undergo BMD testing in the following situations:Females and males 50–64 years old with a previous osteoporosis-related fracture or ≥ 2 clinical risk factors.Patients ≥ 65 years of age with one additional risk factorPatients 70 years of age or older.10Additional patients who may be considered for BMD testing are women who smoke, individuals with > 10% weight loss since the age of 25 (note: medications for weight loss use are on the rise), and those with disorders or medications that increase bone loss.10Bone health and fracture prevention strategies in women ≥ 50 years oldExercise In the scope of osteoporosis prevention and women’s health, the pivotal role of exercise cannot be overstated. As women navigate the transition through menopause, incorporating regular physical activity becomes a potent defence against osteoporosis-related falls and fractures. The decline in estrogen levels during menopause also results in loss of lean muscle and increased weight gain as well as redistribution of body fat often resulting in increased abdominal obesity.11 Abdominal obesity is linked to cardiovascular disease, which is the number one cause of death in women.12 This further underscores the benefit of exercise and a balanced diet for weight management and heart health, in addition to bone health.Studies have shown that postmenopausal women who engage in weight-bearing exercises, such as walking or resistance training, experience not only improved bone density but also enhanced muscle coordination and strength.13 Exercise has also been linked to better cardiovascular health, improved mood and reduced risk of chronic conditions, making it a holistic and indispensable strategy for women’s well-being during this pivotal stage of life.If a patient who has never previously exercised would like to begin, for their safety it is advisable to have their primary care provider clear them for physical activity by using a Physical Activity Readiness Questionnaire (PAR-Q+ Form, see Box 1). The Canadian osteoporosis guidelines recommend two or more exercise sessions per week, which include balance and strength training.14 Balance training can reduce the risk of falls and has the added benefit of improving mental fitness, another important component of aging well.15 A variety of exercises and intensities are encouraged with an emphasis on functional movements, balance and strength. Health Canada recommends ≥ 150 minutes of moderate intensity exercise per week.16Referral to an exercise specialist is advised for exercise recommendations in those with a previous hip fracture or a 10-year fracture risk of ≥ 20% as assessed by FRAX or CAROC.17 A bone fit provider, physiotherapist, athletic therapist or other professional can be consulted to practise safe movements. It is important to note that movements that are repetitive, rapid, sustained, weighted or end of range motion that include twisting and flexion of the spine can potentially increase the risk of spinal fractures and may need to be modified or avoided particularly in those with increased fracture risk.17 Too Fit to Fracture (see Box 1) is an excellent resource provided in print and in video form; it demonstrates spine-sparing movement strategies that are essential for everyone to ensure a healthy spine.Weight-bearing exercises strengthen the skeleton; therefore, it is important to help patients identify which exercises are classified as such. Although a wide variety of exercises are excellent for health and encouraged, some exercises such as swimming and seated cycling are not weight-bearing exercises and, therefore, do not significantly increase bone strength. A progressive approach to exercise is recommended to maintain and improve physical fitness. This can be done by increasing all of the following: exercises requiring balance, weight used for strength training, and increasing volume (repetitions, sets).17NutritionOptimizing nutrition significantly impacts women’s health. For general information on a balanced diet, patients can be directed to Canada’s Food Guide (see Box 1), which provides a brightly coloured image deftly highlighting the breakdown of nutrients using a plate. A diet that contains colourful fruits and vegetables, whole grains, monounsaturated fatty acids and lean proteins provides essential nutrients that are necessary for gut, brain, heart and bone health as well as overall wellbeing.Calcium is a fundamental building block which contributes to bone density and also plays a vital role in muscular function, nerve transmission and cardiac conduction. Health Canada’s recommended dietary allowance for calcium in women > 50 years of age is 1200 mg/day.18 Ideally, this 1200 mg is obtained from dietary sources throughout the day. The benefit of obtaining calcium from food sources (as opposed to supplements) is the added nutrition attained. For example, 3 oz (85 g) of canned salmon with bones contains protein and omega-3 fatty acids, as well as calcium. Patients can be directed to the Osteoporosis Canada website to use the “Calcium Calculator” (see Box 1). Using this interactive and helpful tool, patients can check off the foods they eat in a day. The tool will calculate the total daily amount of calcium and indicate the remaining amount of calcium required for ingestion.When adequate calcium cannot be obtained through diet, calcium supplements should be considered. When helping your patient choose a calcium supplement, consider whether acid-reducing medications are being taken (e.g., proton pump inhibitors [PPIs]) and inquire about antacid use. While calcium carbonate has the most elemental calcium per tablet, calcium citrate is more readily absorbed in patients taking acid-reducing medications.19 Calcium can also interact with several medications, such as levothyroxine, and fluoroquinolone and tetracycline antibiotics, by chelation, therefore reducing absorption. Calcium carbonate was shown to reduce the bioavailability of ciprofloxacin by 40%, which can impair treatment of an infection.20Vitamin D is an essential regulator of bone health and metabolism, with the regulation of calcium absorption of critical importance for bone health. Health Canada’s Recommended Dietary Allowance for vitamin D is 600 IU/day for women > 51 years of age.21 Health Canada recommends patients over 50 years of age take a vitamin D supplement of 400 IU/day, in addition to consuming vitamin D-rich foods.22 Vitamin D is a fat-soluble vitamin that influences the immune system, cardiovascular system, muscles and brain, and supports bone health. A fat-soluble vitamin, it is best absorbed after a meal.Other The 2023 Canadian osteoporosis guidelines state that for people who follow Canada’s Food Guide, no supplementation of protein, vitamin K or magnesium is recommended.10PharmacotherapyA careful review of the patient’s age, risk factors, BMD and FRAX score will determine which patients would benefit from pharmacotherapy, in addition to nonpharmacologic treatments such as nutrition and exercise. An algorithm illustrating the approach to risk factor assessment and pharmacotherapy according to current Canadian guidelines is available online (see Figures 1 and 2 at https://www.cmaj.ca/content/195/39/E1333 ).10Bisphosphonates The 2023 Canadian osteoporosis guidelines prioritize bisphosphonate use for a duration of three to six years as the primary pharmacotherapeutic intervention for the management of osteoporosis. This is consistent with guidelines by the American College of Physicians and the UK National Osteoporosis Guidelines group.23,24 The various available bisphosphonates have different routes of administration and dosing schedules. Oral formulations should be taken with the patient upright (sitting or standing) for at least 30 minutes, with a glass of water to avoid esophageal irritation. The delayed-release formulation of risedronate can be taken with food, but should not be taken concurrently with PPIs as they may increase the serum concentration of risedronate.25When discussing bisphosphonate side effects with patients, it is helpful to put into perspective the frequency of rare but serious side effects such as atypical femur fracture (AFF) and osteonecrosis of the jaw (ONJ). Patients should be reassured that they are 100 times more likely to avoid a fracture with bisphosphonate therapy than they are to experience a serious side effect.26 The risk of AFF and ONJ is minimized when the duration of bisphosphonate therapy does not exceed the recommended three to six years.Denosumab Denosumab subcutaneous injection is recommended for patients who have contraindications or significant intolerance to bisphosphonates. There is a risk of hypocalcemia, especially in patients with a vitamin D deficiency. Canadian product monographs for Prolia and the biosimilar, Jubbonti, recommend monitoring of calcium levels before each dose and within two weeks after the initial dose in patients predisposed to hypocalcemia.27,28 It is important to counsel patients taking denosumab about adherence to the every-six-months dosing schedule. The injection should not be delayed by more than one month because of the risk of rapid bone loss and vertebral fractures.29Menopausal Hormone therapy (MHT) Postmenopausal women suffering from vasomotor symptoms who prioritize alleviation of symptoms affecting their quality of life can consider MHT as an alternative to bisphosphonate therapy when they are < 60 years of age or within 10 years of their last menstrual period and have no other contraindications to MHT.10Other agents For postmenopausal women at risk of breast cancer, raloxifene may be considered, with awareness of possible side effects, such as hot flashes and increased risk of venous thromboembolism.30 In females who have a higher risk of fractures (e.g., recent severe vertebral fracture, or > 1 vertebral fracture and T-score ≤ −2.5), there is evidence showing that anabolic therapy (teriparatide or romosozumab) results in greater reductions in fractures than bisphosphonates.31Pharmacist’s roleMenopause is a time where women may visit their healthcare provider to discuss any number of issues, such as hot flashes, osteoporosis or dyspareunia. These patients would benefit from a review of all risk factors and relevant symptoms during this life stage. Pharmacists are in an ideal position to recognize women at higher risk for osteoporosis and can encourage prevention and management strategies. For example, providing education on spine-sparing exercise strategies not only benefits bone density, but also plays a pivotal role in improving mental health, mobility, self-esteem, autonomy and quality of life. This proactive role helps ensure that women who are navigating through menopause can receive the comprehensive support needed for a healthier and more fulfilling life.Pharmacists can also play a key role and are well-positioned to screen patients for risk factors associated with osteoporosis, reduce the risk of fractures and offer interventions (exercise, nutrition, lifestyle education) to optimize bone health in a collaborative care model with other healthcare providers.Pharmacists can help their patients understand evidence-based recommendations for pharmacotherapy and provide counselling on possible side effects and their management, best practices for administration (e.g., taking bisphosphonates on an empty stomach, upright, with a glass of water), as well as underscoring the importance of adherence, especially with a medication such as denosumab where there is a clear risk of harm in the form of spontaneous vertebral fractures when treatment is delayed. Pharmacists can also collaborate with primary care providers on medication management and monitoring parameters.SummaryA holistic approach to women’s health includes a thorough review of the physiological changes occurring over time and encouraging patients to embrace lifestyle measures for better health and wellness. Empowering our patients involves raising awareness about osteoporosis prevention strategies, guiding them to adopt lifestyle measures that contribute to overall health and wellness, and discussing pharmacotherapy and clinical pearls where appropriate.Sandra Tadros Guirguis (sandra@stgwellness.ca) is a clinical pharmacist, public and corporate speaker, author, personal trainer, certified healthy eating and weight- loss coach, and a Bone Fit Certified Provider in Toronto, ON.References:Osteoporosis Canada. Facts and stats. (accessed August 21, 2024).Government of Canada. Osteoporosis and related fractures in Canada: Report from the Canadian Chronic Disease Surveillance System 2020. (accessed August 21, 2024).Lu PW, Briody JN, Ogle GD, et al. Bone mineral density of total body, spine, and femoral neck in children and young adults: a cross-sectional and longitudinal study. J Bone Miner Res 1994;9(9):1451-8. doi:10.1002/jbmr.5650090918.Zhu X, Zheng H. Factors influencing peak bone mass gain. Front Med 2021;15(1):53-69. doi:10.1007/s11684-020-0748-y.Sabatier JP, Guaydier-Souquières G, Laroche D, et al. Bone mineral acquisition during adolescence and early adulthood: a study in 574 healthy females 10-24 years of age. Osteoporos Int 1996;6(2):141-8. doi:10.1007/BF01623938.Bachrach LK. Hormonal contraception and bone health in adolescents. Front Endocrinol 2020;11:603. doi:10.3389/fendo.2020.00603.Agostino H, Di Meglio G. Low-dose oral contraceptives in adolescents: how low can you go? J Pediatr Adolesc Gynecol 2010;23(4):195-201. doi:10.1016/j.jpag.2009.11.001.Crandall CJ, ed. Menopause practice: a clinician’s guide. 6th ed. North American Menopause Society; 2019.International Osteoporosis Foundation. World Osteoporosis Day, Campaign Took Kit. (accessed August 21, 2024).Morin SN, Feldman S, Funnell L, et al. Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update. Can Med Assoc J 2023;195(39):E1333-E1348. doi:10.1503/cmaj.221647.Ko SH, Jung Y. Energy metabolism changes and dysregulated lipid metabolism in postmenopausal women. Nutrients 2021;13(12):4556. doi:10.3390/nu13124556.Vogel B, Acevedo M, Appelman Y, et al. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. Lancet 2021;397:2385-2438. doi:10.1016/S0140-6736(21)00684-X.Capel-Alcaraz AM, García-López H, Castro-Sánchez AM, et al. The efficacy of strength exercises for reducing the symptoms of menopause: a systematic review. J Clin Med 2023;12(2):548. doi:10.3390/jcm12020548.Osteoporosis Canada. Too fit to fall or fracture. (accessed August 21, 2024).Harvard Health Publishing. Body and brain and crucial to good balance. June 18, 2021. (accessed August 21, 2024).Government of Canada. Physical activity and your health. (accessed August 21, 2024).Osteoporosis Canada. Too fit to fracture. Evidence-based recommendations to help reduce the risk of fractures. (accessed August 21, 2024).Government of Canada. Seniors and aging–osteoporosis. (accessed August 21, 2024).Harvard Health Publishing. Choosing a calcium supplement. October 13, 2020. (accessed August 21, 2024).Frost RW, Lasseter KC, Noe AJ, et al. Effects of aluminum hydroxide and calcium carbonate antacids on the bioavailability of ciprofloxacin. Antimicrob Agents Chemother 1992;36(4):830-2. doi:10.1128/AAC.36.4.830.Osteoporosis Canada. Vitamin D. (accessed August 21, 2024).Government of Canada. Vitamin D. (accessed August 21, 2024).Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, et al. Clinical Guidelines Committee of the American College of Physicians. Pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults: a living clinical guideline from the American College of Physicians. Ann Intern Med 2023;176(2):224-38. doi:10.7326/M22-1034.Gregson CL, Armstrong DJ, Bowden J, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2022;17(1):58. doi:10.1007/s11657-022-01061-5UpToDate. Drug interaction tool. (accessed August 26, 2024).Osteoporosis Canada. 2023 Starting medication. (accessed August 21, 2024).Amgen Canada Inc. Prolia (denosumab injection) product monograph. Mississauga, ON; November 24, 2023. https://pdf.hres.ca/dpd_pm/00073837.PDF (accessed August 21, 2024).Sandoz Canada Inc. Jubbonti (denosumab injection) product monograph. Boucherville, QC; February 16, 2024. (accessed August 27, 2024).Amgen. Prolia Health Care Provider Site. Published online 2017. AACE guidelines: no drug holiday recommended for Prolia. (accessed August 21, 2024).Shoback D, Rosen CJ, Black DM, et al. Pharmacological management of osteoporosis in postmenopausal women: an Endocrine Society guideline update. J Clin Endocrinol Metab 2020;105(3):587-94. doi:10.1210/clinem/dgaa048.Bandeira L, Lewiecki EM. Anabolic therapy for osteoporosis: update on efficacy and safety. Arch Endocrinol Metab 2022;66(5):707-16. doi:10.20945/2359-3997000000566.

Osteoporosis in women

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