Management of male osteoporosis in primary care: clinical approach and pharmacotherapy

Opening Vignette Mr Loh is a 69-year-old retired engineer with a history of hypertension and newly diagnosed high-grade, locally advanced, non-metastatic prostate cancer. He is scheduled to start on androgen deprivation therapy. He presents to your clinic to discuss screening for bone health, as he has heard that the medication used for his prostate cancer may increase the risk of osteoporotic fractures.WHAT IS MALE OSTEOPOROSIS? Osteoporosis is a condition of decreased bone mass leading to an increased risk of fragility fractures. It has been traditionally viewed as a disease of postmenopausal women. However, research shows that this disease also causes a substantial health burden in men. It is estimated that after the age of 50 years, one in five men will experience an osteoporotic fracture in their lifetime.[1] Globally, 39% of osteoporotic fractures occur in men.[2] Mortality is higher in males who suffer osteoporotic fractures than in females. Worldwide, men face a 1.3–2-fold higher mortality risk after a hip or vertebral fracture, a difference that may be due to increased infection rates and multimorbidity in men.[3,4] Locally, a cohort study conducted at the Singapore General Hospital in 2007 showed a calculated 1-year mortality rate of 32.0% for males following a hip fracture, compared to 24.4% for females.[5] WHAT CAUSES MALE OSTEOPOROSIS? Low bone mass in men can generally be attributed to one or more of the following factors: (a) suboptimal peak bone mass acquisition (80% of peak bone mass is genetically determined; environmental factors such as poor nutrition and decreased physical activity can contribute to suboptimal peak bone mass[6]); (b) ongoing bone loss (contributed by secondary causes of osteoporosis, e.g. heavy smoking, excess alcohol (ETOH) intake, long-term glucocorticoid exposure); or (c) reduced bone formation (e.g. androgen deficiency or ageing). Women experience a period of rapid decline in bone mineral density (BMD) after menopause due to the loss of ovarian oestrogens. In men, however, age-related gonadal decline is much more gradual. HOW RELEVANT IS THIS TO MY PRACTICE? Primary care physicians are ideally equipped to identify male patients at risk of osteoporosis, due to their role as the first point of contact in healthcare, coupled with the close relationships and long-term continuity of care with their patients.[7] This allows for personalised care and better identification of risk factors over time. With the introduction of Healthier SG,[8] the increased focus on preventive care will empower primary care physicians to educate men about lifestyle changes that can enhance bone health, such as smoking cessation, diet and exercise. By coordinating care with specialists, when necessary, primary care physicians can ensure a comprehensive approach to osteoporosis management. WHAT CAN I DO IN MY PRACTICE? Primary care physicians should be on the lookout for osteoporosis in all male patients, starting from age 65, or younger if significant risk factors are present.[9] Several guidelines have also proposed performing a clinical risk assessment for all males starting from age 50 to guide the need for further BMD testing.[10,11] Physicians should consider performing a dual-energy X-ray absorptiometry (DXA) BMD test for males aged ≥65 years if they have risk factors for low bone mass. They should also consider the test for those aged <65 years if they have significant risk factors, such as low bone mass due to the use of long-term steroids, androgen deprivation therapy or medical conditions associated with bone loss, including hypogonadism or hyperthyroidism, and the presence of a fragility fracture (sustained from minimal or no identifiable trauma, excluding skull, facial bone, metacarpal, metatarsal and phalangeal fractures). Finally, physicians should counsel patients on early modification of risk factors, such as low body mass index (BMI), smoking, alcohol consumption and sedentary lifestyle. Fracture risk assessment using FRAX® Primary care physicians should consider performing a fracture risk assessment using FRAX®, a computer algorithm designed by the Sheffield World Health Organization Collaborating Centre for Metabolic Bone Diseases. It calculates the 10-year probability of a fracture based on easily obtainable clinical risk factors, and can be used with or without a BMD measurement. Clinical approach Research indicates that secondary and senile forms of osteoporosis predominate in men, whereas postmenopausal osteoporosis is the most common form in women.[12] Worldwide studies indicate that approximately 40%–60% of men with osteoporotic fractures have an identifiable secondary cause.[13,14] Hence, physicians should carefully assess the presence of secondary causes for osteoporosis and risk factors for osteoporotic fractures in males [Boxes 1 and 2].[15,16]Box 1: Risk factors and secondary causes of male osteoporosis.Box 2: History taking and physical examination.Diagnosis It is recommended that the same reference range for T-scores be used in both males and females. For men aged <50 years, physicians should use the Z-score instead of the T-score to guide management [Table 1].Table 1: Interpretation of bone mineral density.[ 17 ]Investigations It is important to have a higher index of suspicion for secondary causes of osteoporosis in males, especially in the absence of traditional risk factors for osteoporosis. An age-stratified approach can be considered when deciding what investigations should be performed. For males aged <50 years, a referral to an endocrinologist is recommended for more extensive secondary workup, including assessing for the presence of hypogonadism and its causes (e.g. low testosterone levels). For males aged between 50 and 70 years, consider a referral for more extensive secondary workup if this is suspected based on history and physical examination. For males aged ≥70 years, consider baseline investigations [Box 3] for secondary osteoporosis in the primary care setting, such as with corrected calcium, creatinine, 25-hydroxyvitamin D (25-OH vitamin D), thyroid function test (TFT), full blood count (FBC), ± alkaline phosphatase (ALP) and serum phosphate.Box 3: Investigations.Management in primary care Non-pharmacological management is recommended for all males at risk of or diagnosed with osteoporosis, and it is similar to the recommendations for females. These include maintaining a diet with adequate calcium and vitamin D, engaging in weight-bearing and resistance exercises, avoiding known osteoporosis risk factors such as smoking and excessive alcohol, and maintaining good dental hygiene. Pharmacological options for males are summarised in Box 4.Box 4: Pharmacological options.In recent years, there is increasing interest in anabolic therapies such as teriparatide and romosozumab. Studies have shown that osteoanabolic therapies are more effective at increasing BMD over a shorter period compared to oral antiresorptive medications. Recognising the need for more urgent interventions in patients at very high risk of fracture, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and International Osteoporosis Foundation (ESCEO-IOF) recommends stratifying treatment according to fracture risk in individuals. This requires considering if a patient would fall into ‘high risk’ and ‘very high risk’ categories, whereby those at very high risk may be offered anabolic agents before starting antiresorptive therapies.[20] Research has also shown that fracture risk is highest immediately after a sentinel fracture and wanes over time.[21] In the recent Singapore Agency for Care Effectiveness guidelines for diagnosis and management of osteoporosis, patients at very high risk of fractures are defined as those with very low BMD (T-score ≤−3.0), and those with ≥2 vertebral fractures or ≥2 fragility fractures.[9] For patients with very high fracture risk, consider a discussion about the possibility of commencing anabolic or parenteral treatment as the first-line treatment. Patients who are keen to commence parenteral treatment can be referred to a specialist for further management. As the osteoanabolic agents, teriparatide and romosozumab, are non-standard drugs, patients should be counselled on their estimated cost before referral. In Singapore, the Ministry of Health’s Drug Advisory Committee has recommended teriparatide biosimilar (Sondelbay) 600 mcg/2.4 mL injection to be included on the Medication Assistance Fund subsidy status from 1 August 2025.[22] Role of testosterone therapy Testosterone therapy is used to treat symptoms of hypogonadism. Testosterone treatment may have skeletal benefits in men with serum testosterone levels below the normal range and should be used in individuals with congenital hypogonadism and some instances of acquired hypogonadism. In males with functional hypogonadism (i.e. age-related decline in testosterone), the effects of testosterone administration on fracture risk remain uncertain and it has not been shown to reduce fracture risk. Treatment with testosterone in older males also carries increased risk of cardiovascular disease and prostate cancer. Hence, testosterone replacement is appropriate only in men with lower risk who may benefit from relief of hypogonadal symptoms. The Endocrine Society recommends the addition of a pharmacological agent with proven anti-fracture efficacy (e.g. a bisphosphonate or teriparatide) to testosterone-treated hypogonadal men at high risk of fracture.[23] In healthy men without hypogonadism, testosterone therapy is not an approved osteoporosis treatment for reducing fracture risk. In men with high fracture risk, non-hormonal pharmacotherapy (e.g. with oral bisphosphonates) should be offered. Indications for referral Primary care providers should consider referral to a specialist for male osteoporosis patients aged <50 years, those with signs or symptoms suggestive of hypogonadism and who are suitable candidates for testosterone therapy, and males suspected of having a secondary cause of osteoporosis, for which evaluation or management cannot be performed in primary care. Of note, males who are not suitable candidates for testosterone therapy include those at high cardiovascular risk (e.g. acute myocardial infarction or stroke within the past 6 months), heart failure or untreated severe obstructive sleep apnoea; those with breast cancer, known prostate cancer, a palpable prostate nodule or induration, or elevated prostate specific antigen; those with severe lower urinary tract symptoms suggestive of prostatism; those with elevated haematocrit or thrombophilia; and those planning fertility in the near term. Men at very high risk of fracture who are suitable for anabolic agents, with progression of bone loss (BMD decline exceeding the least significant change) or recurrent fractures while on treatment, would also benefit from specialist referral. TAKE HOME MESSAGES Osteoporosis in men is often underdiagnosed and undertreated, despite evidence showing a substantial health burden in this population. Fragility fractures have a higher mortality rate in males compared to females. Physicians should assess the risk profile for osteoporosis in men aged ≥65 years and consider referral for those at high risk for DXA BMD. Owing to the higher prevalence of secondary osteoporosis in men, a higher index of suspicion for secondary causes is required. Common causes of secondary osteoporosis in males include endocrine causes (e.g. hypogonadism), medications and alcohol use. Males suspected to have hypogonadism and are suitable candidates for testosterone replacement therapy should be referred to an endocrinologist for further evaluation. Most males aged >70 years with osteoporosis can be managed in primary care. Non-pharmacological management focuses on addressing lifestyle factors that lead to bone loss, such as smoking, excessive alcohol consumption, physical inactivity and inadequate nutrition. Pharmacological treatment options should be evaluated based on fracture risk. For patients at very high fracture risk, physicians should discuss the possibility of commencing anabolic or parenteral treatment as a first-line treatment. Patients keen to commence parenteral treatment may be referred to a specialist for further management. Male patients with osteoporosis who are managed in primary care can be treated with oral bisphosphonates. Closing Vignette Further history reveals that Mr Loh has a 40 pack-year smoking history, no prior fractures and a maternal history of hip fracture at age 80. Physical examination shows dental caries. His BMI is in the healthy range, and his fall risk is low. Given his increased risk of osteoporosis, you arrange a DXA scan and baseline bone health investigations. Mr Loh’s DXA results show a femoral neck T-score of –3.3 and a Z-score of –1.9, and his 25-OH vitamin D is low at 13 ng/mL. Corrected calcium level is 2.2 mmol/L, and a recent bone scan excluded bony metastases. You determine that his osteoporosis is attributed mainly to smoking and vitamin D deficiency. You counsel smoking cessation, refer him for dental review in preparation for antiresorptive therapy, and arrange for dietitian input to optimise calcium, vitamin D and protein intake, together with oral calcium and vitamin D supplementation. You assess Mr Loh to be at high risk of fracture and explain that androgen deprivation therapy may further reduce bone mineral density. After discussing the risks and benefits of treatment, you refer him to an endocrinologist for consideration of parenteral therapy.Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. SMC CATEGORY 3B CME PROGRAMME Online Quiz: https://www.sma.org.sg/cme-programme Deadline for submission: 6 pm, 28 March 2026