Article Archive
May/June 2024

May/June 2024 Issue

Not a Women’s Disease
By Mark D. Coggins, PharmD, BCGP, FASCP
Today’s Geriatric Medicine
Vol. 17 No. 3 P. 22

Osteoporosis in Men Is on the Rise

Osteoporosis is a “silent disease” characterized by reduced bone mass and poor bone quality, which increase the propensity for osteoporotic fractures associated with reduced quality of life due to disability, acute and chronic pain, more frequent hospitalizations, and increased risk of death. Osteoporosis has traditionally been considered a female health issue associated with the postmenopausal effects the loss of estrogen has on decreased bone mass. However, while osteoporosis is more common in females, there’s been an increase in osteoporosis burden and associated fragility fractures in men over the past decades, likely due to increased life expectancy, more sedentary lifestyles, and increased prevalence of risk factors.1 Furthermore, osteoporosis mortality and morbidity rates are higher in men than women.2 Men are also twice as likely to die in the hospital following a hip fracture than are females.3 Of additional concern is that the consequences of osteoporosis in men are underestimated, and the condition is often unrecognized and untreated in most men.4

As the population continues to age rapidly, osteoporosis in men will become an even more significant public health issue. Increased awareness about osteoporosis in males is needed, making it imperative for health care professionals to understand the causes and risk factors, screening recommendations, and prevention and treatment strategies so that they educate and assist male patients in minimizing their risk for adverse osteoporosis-related outcomes. (See the sidebar for statistics about osteoporosis in men.5)

Bone Remodeling
Bone remodeling consists of a resorption phase where osteoclasts digest old bone, followed by a formation phase in which osteoblasts lay down new bone and subsequently become mineralized. Bone remodeling allows bones to remain healthy and strong while also supplying calcium to the body. Remodeling continues throughout life, replacing most of the adult skeleton every 10 years.6

Peak Bone Mass
Peak bone mass (PBM) is the maximum amount of bone a person will ever have. Bone development begins in childhood and increases dramatically during puberty, when the largest gains in PBM occur. Bone mass continues to build after puberty, with most people reaching their PBM around their mid-20s. PBM in men is about 8% to 10% higher than in females.1 Men have a lower risk of osteoporosis and fragility fractures primarily due to women having bones with smaller diameters, lower PBM, a menopause-related bone resorption, and a higher risk of falls than men.7

As the time to develop PBM is limited, education on bone health and the importance of PBM should occur during childhood, adolescence, and young adulthood. Maximizing PBM is critical to reducing osteoporosis-associated fragility fractures later in life, as an increase of PBM by 10% reduces the risk of fragility fractures by 50%.8 Education should include the importance of proper nutrition, including adequate calcium and vitamin D intake, the need for weight-bearing exercise, and how lifestyle choices such as smoking, alcohol use, and even excessive soda intake can negatively influence PBM and bone strength.

In osteoporosis, an imbalance in remodeling results in the body making too little bone, losing too much bone, or both. Subsequently, the bone becomes brittle and weak, which increases the risk of fractures and associated complications, including limited mobility, depression, pain, cardiovascular disease, and tremendous costs to society.9 No one factor is responsible for osteoporosis in males. Instead, it occurs due to the interplay of multiple factors, which may include increasing age and associated sex hormone deficiencies (eg, testosterone), genetics, ethnicity, poor nutrition, lifestyle choices (eg, physical inactivity, tobacco use, and excessive alcohol intake), and specific factors including comorbid diseases (eg, hypogonadism, hyperthyroidism) and medications (eg, corticosteroids) that cause bone loss.10

Role of Sex Hormones
The association between bone loss and age is well documented, and the incidence of osteoporotic fractures increases exponentially with age. Bone mass typically stays constant until around age 35, when bone loss starts as the degradation of bone begins to exceed the amount of new bone created. During the first five to six years of menopause, the sharp decline in estrogen results in an average 10% reduction in bone mass, with approximately half of women losing 10% to 20% of BMD.11 As men get older, production of estradiol and testosterone decreases, but unlike in women, the decline is slower and steadier. Because men have greater initial PBM than do women, slower bone loss, and a smaller overall decrease in BMD, the time to reach peak fracture risk starts approximately 10 years later in men than in women.12

No symptoms of osteoporosis may be seen until a fracture has already occurred. Additionally, osteoporotic bones are so weak that minimal trauma fractures can occur with little or no trauma. For instance, fractures may occur from a fall from a standing height that would not usually cause a break in healthy bones, or they may occur under normal stresses such as bending, lifting, or even coughing. Symptoms that may indicate a vertebral fracture include severe back pain, loss of height, or spine malformations such as a stooped or hunched posture (kyphosis).

Risk Factors
Common risk factors for osteoporosis and osteoporotic fractures in males include advanced age (older than age 70), non-Hispanic white and Asian ethnicity, thin body build, family history of osteoporosis, prior fractures, falls, hypogonadism (low testosterone), chronic disease (eg, dementia, diabetes, rheumatoid arthritis, and hyperthyroidism), inadequate nutrition (low vitamin D levels, inadequate calcium intake), lifestyle choices such as smoking, excessive alcohol use, obesity, lack of exercise, and some medications including glucocorticoids, anticonvulsants, proton pump inhibitors, thiazolidinediones (diabetes medication), antidepressants, loop diuretics, vitamin A and synthetic retinoids, antiretrovirals, and chemotherapeutic drugs (eg, methotrexate). About 50% to 65% of the condition in males diagnosed with osteoporosis may occur secondary to metabolic diseases, toxic substances, or iatrogenic side effects of medications.13

Calcium and Vitamin D
Ensuring adequate calcium and vitamin D is necessary for good bone health. Calcium deficiency contributes to diminished bone density, early bone loss, and increased fracture risk. Vitamin D is essential across all ages, contributing to the development of PBM in younger individuals, while low levels of vitamin D in adults can lead to loss in bone mass and subsequent osteoporosis. Calcium alone or in combination with vitamin D has been shown to reduce fracture risk by 12% in men and women 50 years of age and older.14

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 daily in men 71 and older.15 Adequate vitamin D is needed to absorb calcium. The RDA for vitamin D is 600 IUs (international units) per day in men ages 19 to 70. The recommendation increases to 800 IUs daily for men ages 71 and older.16

Screening and Diagnosis
Dual-energy X-ray absorptiometry (DEXA) scanning of the hip and spine is the gold-standard test used to measure bone mineral density (BMD) and diagnose osteoporosis. DEXA measures the amount of calcium and other minerals in a specific area of the bone. Most guidelines recommend testing men 70 years or older and men 50 to 69 years old if risk factors are present.

Screening tools like the Fracture Risk Assessment Tool (FRAX) may also be used with BMD. FRAX is a screening tool that calculates the risk of a 10-year probability of hip fracture and major osteoporotic fracture (hip, spine, proximal humerus, or forearm) for untreated patients from 40 to 90 years of age.17 Clinical risk factors included in the calculation are age, gender, weight, height, previous fracture, parent fractured hip, current smoking, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, and alcohol (three or more units per day).

Pharmacological treatment is recommended for men 50 years and older who present with any of the following: hip or vertebral fracture, T-score of −2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes, or low bone mass (T-score between −1.0 and −2.5 at the femoral neck or spine) and a 10-year hip fracture risk of at least 3% or a 10-year major fracture risk of at least 20% (as calculated using the FRAX).18

Bisphosphonates are antiresorptive agents and are recommended as first-line treatment to reduce the risk of vertebral fractures in men with clinically recognized osteoporosis. Bisphosphonates are also effective in men with bone loss from secondary causes, such as corticosteroid use, androgen deprivation therapy, rheumatologic disorders, and hypogonadism.3 FDA-approved bisphosphonates for male osteoporosis include the oral agents alendronate and risedronate, and zoledronic acid—an IV formulation. All three are effective in reducing vertebral and hip fractures.19 In male patients, in order to prevent one vertebral fracture using bisphosphonates, it would be necessary to treat 16 patients for a two-year period.20

Teriparatide (Forteo)
Teriparatide is a parathyroid hormone analog and potent anabolic that increases calcium absorption in the intestines, reduces bone turnover, increases the formation of new bone, and increases BMD and bone strength.21 Teriparatide is indicated in men who have severe osteoporosis or multiple fracture risk factors or in those for whom treatment with bisphosphonates has failed. Teriparatide is administered subcutaneously daily, and it is recommended that teriparatide use be limited to two years. There is good evidence that teriparatide increases BMD at the lumbar spine and femoral neck in men with osteoporosis.

Abaloparatide (Tymlos)
Abaloparatide is an analog of parathyroid hormone-related peptide [PTHrP(1-34)]. The anabolic effects of abaloparatide result in increased BMD and bone mineral content, thereby increasing bone strength at vertebral and nonvertebral sites. On December 19, 2022, the FDA approved abaloparatide for the treatment of men with osteoporosis at high risk of fracture, as well as adult patients for whom other osteoporosis therapies have proved ineffective and those can’t tolerate other therapies.22 Abaloparatide was previously only approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture.

The approval of abaloparatide in men was based on a multicenter phase 3 study, randomized and double-blinded.22 For the study, a group of men with osteoporosis (N=149) aged 40 to 85 were given abaloparatide daily as a subcutaneous injection. This group was compared with men with osteoporosis (N=79) who received placebo injections. Both groups received vitamin D and calcium supplements. At month 12, treatment with abaloparatide significantly increased BMD at the lumbar spine, total hip, and femoral neck, compared with placebo. For the primary efficacy measure of the lumbar spine, the change in percentage in BMD from baseline was 8.5% for patients treated with abaloparatide and 1.2% for the placebo group—a 7.3% treatment difference.

Denosumab (Prolia)
Denosumab is a RANK ligand inhibitor that inhibits osteoclast formation; decreases bone breakdown, bone loss, and bone pain; increases BMD; and reduces fracture risk.24 It’s indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture, defined as those having a history of osteoporotic fracture or multiple risk factors for fracture, and for patients who have failed or are intolerant to other available osteoporosis therapies. It’s administered as a subcutaneous injection once every six months.

Research has shown that Prolia significantly increased BMD in men by 8.8% at the lumbar spine, 6.4% at the total hip, and 5.2% at the femoral neck in trials that measured BMD after three years of treatment with Prolia.25 Consistent effects were seen in all ages and races regardless of weight/body mass index, baseline BMD, or level of bone turnover. Once Prolia was stopped, BMD returned to approximately baseline levels within 12 months.

Romosozumab (Evenity)
Romosozumab was approved in 2019 and is the newest bone-building medication to treat osteoporosis. It is a humanized monoclonal antibody that inhibits sclerostin, a protein involved in regulating bone formation. It has a dual effect on bone, increasing bone formation and decreasing bone resorption. Romosozumab is only FDA-approved for women with a history of osteoporotic fracture or multiple risk factors for fracture and those who have failed or are intolerant to other osteoporosis therapies.26,27 However, there’s limited data on its safe and effective use in men with a previous fracture who have failed or cannot otherwise use other agents. In a phase III clinical trial, romosozumab was administered to men aged 55 to 90 through subcutaneous injection monthly for 12 months and was compared with a matched placebo for the 12-month treatment period. The results demonstrated a statistically significant increase in BMD at the lumbar spine (primary endpoint) and the femoral neck and total hip (secondary endpoint).28

One dose consists of two subcutaneous injections, one immediately following the other, given once a month by a health care professional. Romosozumab should only be taken for one year because its bone-forming effect wanes after 12 months. Romosozumab carries a black box warning for the potential risk of myocardial infarction, stroke, and cardiovascular death. For that reason, careful patient selection is warranted, and the use of romosozumab should be avoided in patients who have had a heart attack or stroke within the previous year.27

In men, osteoporosis may be linked to an age-related decline in testosterone levels or hypogonadism, making it a potential treatment option. Testosterone’s direct effects via the androgen receptor on osteoblasts promote trabecular bone formation.29 A meta-analysis of eight trials enrolling 365 men showed that intramuscular testosterone was associated with an 8% gain in lumbar BMD compared with placebo.30

Increasing Awareness
Osteoporosis in males is a growing health care concern and requires that health care professionals take steps to increase awareness about the condition. Opportunities to educate males about the importance of bone health exist across age groups, including the very young. Men at high risk should be screened, and those with osteoporosis should be encouraged to consider pharmacologic treatments that may help maintain BMD and bone mass, prevent fractures, reduce pain, and allow them to maintain a good quality of life. Providers can also help patients weigh these benefits against the potential side effects that may be associated with osteoporosis medications.

— Mark D. Coggins, PharmD, BCGP, FASCP, is a long term care expert and corporate pharmacy consultant for Touchstone-Communities, a leading provider of senior care that include skilled nursing care, memory care, and rehabilitation for older adults throughout Texas. He’s a past director of the American Society of Consultant Pharmacists and was nationally recognized by the Commission for Certification in Geriatric Pharmacy with the Excellence in Geriatric Pharmacy Practice Award.


According to the Bone Health and Osteoporosis Foundation5:

• As many as 25% of men older than age 50 will break a bone due to osteoporosis.

• Approximately two million American men have osteoporosis, with another 12 million at risk.

• Men older than 50 are more likely to break a bone due to osteoporosis than they are to get prostate cancer.

• Each year, about 80,000 men will break a hip.

• Men are more likely than women to die within a year after breaking a hip, and this is related to problems associated with the break.

• Men can break bones in the spine or break a hip, but this usually occurs at a later age than in women.


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