Osteoporosis in men

doi:10.1016/S2213-8587(22)00012-2

The Lancet Diabetes & Endocrinology

Volume 10, Issue 4, April 2022, Pages 273-283

https://doi.org/10.1016/S2213-8587(22)00012-2 Get rights and content

Summary

Osteoporosis in men is a common but often overlooked disorder by clinicians. The criterion for osteoporosis diagnosis in men is similar to that in women—namely, a bone mineral density (BMD) that is 2·5 standard deviations or more below the mean for the young adult population (aged 20–29 years; T-score –2·5 or lower), measured at the hip or lumbar spine. Sex steroids are important for bone health in men and, as in women, oestrogens have a key role. Most men generally have bigger and stronger bones than women and typically have less bone loss during their lifetime. Men typically fracture less often than women, although they have a higher mortality rate after a fracture. Secondary osteoporosis is more common in men than in women. Lifestyle changes, adequate calcium, vitamin D intake, and exercise programmes are recommended for the management of osteoporosis in men. Bisphosphonates, denosumab, and teriparatide have been shown to increase BMD and are used for pharmacological treatment. In this Review, we report an updated overview of osteoporosis in men, describe new treatments and concepts, and discuss persistent controversies in the area.

Introduction

Osteoporosis increases the risk of fractures and is defined operationally as a bone mineral density (BMD) value that is 2·5 standard deviations or more below the mean for young adults (T-score –2·5 or lower).¹ This overlooked disorder is more common in women, but is also found in men. In this Review on the diagnosis and management of osteoporosis in men, we report an updated overview of the field, describe new treatments and concepts, and discuss persistent controversies.

Section snippets

Epidemiology

In 2015, there were approximately 20 million people in the EU with osteoporosis; 4·2 million of them were men.² The prevalence of osteoporosis in men older than 50 years is 7%, which is lower than the prevalence of 23% reported for women.² As in women, men who have a BMD that is in the osteoporosis range do not always have fractures; between 27% and 45% of fractures in older men (older than 50 years) occurred within those with a BMD range of –1.0 to –2·0.³

The economic burden of fractures in

Mortality

One in 15 patients with hip fracture aged 60 years and older will die during treatment in hospital, with men having higher in-hospital mortality than women (10% vs 5%).⁹ A third of those who survive during hospitalisation will die within a year, with men having higher rates of mortality a year after hip fracture than women (38% vs 28%). Male gender is an independent factor associated with mortality.⁹ Men older than 60 years who have fractured their hip have an 8-fold increase in mortality risk

Bone mass in men

In the first decades of life, the skeleton changes its shape and grows, and bone mass is accrued up to a peak. The magnitude of this peak is influenced by genetic and environmental factors. The difference in peak bone mass between sexes starts during puberty, and peak bone mass is greater in men due to a longer bone maturation period.¹⁷ In addition, studies have shown that androgens stimulate periosteal bone formation in rats, which might also have a role in the sexual dimorphism seen in humans.

Trabecular bone

Age-related bone loss is associated with three main processes: trabecular bone loss, continued net resorption at the endocortical surface, and decrease in cortical volumetric BMD.²⁰

Riggs and colleagues²⁰ have shown that trabecular bone loss begins in early adulthood (21–49 years) in both men and women in cross-sectional and longitudinal studies with central and peripheral quantitative CT (HR-pQCT).²⁴ Men have 42% of their total lifetime trabecular bone loss before the age 50 years.²⁴ The

Imaging osteoporosis in men

There are several recommendations45, 46, 47, 48, 49, 50, 51, 52 for screening osteoporosis in men, which use BMD of the spine and hip. There is a long-standing debate on which database should be used as a reference for the T-score calculation in men (appendix pp 1–3). In summary, testing for osteoporosis has been recommended in men aged 65 years or older by several groups, or earlier if there are risk factors. Vertebral fracture assessment is also usually recommended by some authorities in

Fracture risk assessment in men

Fracture prediction tools can also be used to predict the risk of fractures and identify the need for BMD measurement. There are several tools available in clinical practice, the best-known ones being Fracture Risk Assessment Tool (FRAX),⁵⁴ Garvan,⁵⁵ and QFracture.⁵⁶ These tools can predict the risk of fracture during a 1–10 year period. FRAX and Garvan can incorporate BMD measurements. The femoral neck T-score alone is equally as good as these tools, which were found to be poorly calibrated

Causes of osteoporosis in men

Idiopathic osteoporosis is defined by the development of osteoporosis or fractures before the abnormalities associated with ageing are expected.⁶⁰ Idiopathic osteoporosis is a heterogeneous condition, often associated with family history, where both genetic and environmental factors might have a role. A recent study of a cohort of men with idiopathic osteoporosis identified variants of the LRP5 gene using next-generation sequencing of genes that were potentially linked to low BMD.⁶¹ The product

Bone fragility associated with androgen deprivation therapy

Bone health is an emerging concern in men receiving treatment for prostate cancer. One in eight men will receive a diagnosis of prostate cancer in their lifetime. However, early diagnosis and advances in therapy currently result in an 85% survival rate. This increased survival rate has raised the importance of the long-term consequences of treatment, such as cancer treatment-induced bone loss and the resulting increased risk of fractures.⁶⁶

Continuous or intermittent androgen deprivation therapy

General approach to the management of men with osteoporosis

The management of men with osteoporosis begins by considering the impact of osteoporosis on their health. For example, considering whether they have back pain, height loss, or kyphosis. These considerations are important as they are often the most pressing issues of concern and call for adequate analgesia. Vertebral augmentation might reduce pain early, but the American Society for Bone and Mineral Research Task Force concluded that routine use was not supported by evidence.⁷⁰

The risk factors

Pharmacological therapy

We recommend assessment of fracture risk and specific treatment in men who are at high risk. It is usual to recommend pharmacological therapy in men with a T-score at the spine or hip of –2·5 or less, a history of vertebral, or a history of hip fracture. In some countries (eg, the USA), it is usual to use a 10 year fracture risk at the hip of 3% or more or a 10 year fracture risk of major fractures of 20% or more to recommend therapy,⁴⁶ whereas, in other countries (eg, the UK), it is usual to

Treatment in men receiving ADT

ADT results in accelerated bone loss from the peripheral and central skeleton. Lifestyle changes and adequate calcium and vitamin D intake are recommended in men receiving ADT. Bone loss associated with ADT can be prevented by bisphosphonates. Several clinical trials have shown an increase in BMD with the use of bisphosphonates in men receiving ADT compared with those receiving placebo; however, it is not known whether the incidence of fractures is reduced in men receiving ADT and

Treatment guidance for osteoporosis in men

Bisphosphonates have shown the strongest evidence for treatment efficacy and cost-effectiveness in men and so they are often used as front-line treatment.¹⁰³ If the man is intolerant of oral bisphosphonates, prefers an intravenous treatment, or if treatment is not successful, then zoledronate is recommended. Zoledronate has the advantage of being the only treatment proven to reduce fracture risk in men in a clinical trial.⁹⁹ If the patient develops a vertebral fracture while on treatment, then

Conclusion

In conclusion, men are at risk of fragility fractures and have higher mortality than women after a fracture. We have stressed the importance of identifying secondary osteoporosis and treating contributing conditions. Many of the risk factors for fracture in men are like those in women and advice should be given concerning an adequate diet (eg, for adequate calcium, protein, and vitamin D intake), regular exercise, and avoidance of smoking or excessive alcohol consumption. Anti-resorptive (eg,

Search strategy and selection criteria

We searched MEDLINE for articles published from Jan 1, 2012, to Nov 25, 2021, using the terms “osteoporosis” and “fractures” in combination with terms such as “male” and “men”. Only articles published in English and research in humans were considered. Peer-reviewed full-text articles found in this search, and key references cited in these articles and previous Reviews, were reviewed.

Declaration of Interests

RE reports grants from Amgen, Immunodiagnostic Systems, Alexion, Roche, and Nittobo; and personal fees from IDS, GSK Nutrition, Mereo, Sandoz, Nittobo, Samsung, Haoma Medica, Elsevier, CL Bio, and University of California at San Francisco. TV and MS declare no competing interests.

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Through this study, we assess whether night shift work increases the risk of osteoporosis, and explore the effects of age, gender, or lifestyle differences.
This cross-sectional study included the collection of data from a sample of the US adults who participated in the National Health and Nutrition Examination Survey (NHANES) over a 7.3-year period (2007–2008, 2009–2010, 2017–March2020), including 4408 participants (2351[52.8%] men and 2057[47.2%] women), with an age range of 20–80 years. The primary variables, health status, nutrition, harmful lifestyle habits, and bone mineral density (BMD), were segregated, and analyzed according to different work schedules. Linear regression models were conducted to evaluate correlations of night shift work and T-scores. Associations between night shift work and osteoporosis were examined using logistic regression analyses. All regression models were stratified by gender and age ≥50 years. Osteoporosis was defined as BMD at the femoral neck or total spine equal to or less than 2.5 standard deviations below the mean for youthful people of the same gender. All data were obtained using questionnaires and examinations collected in mobile examination center (MEC) from NHANES.
After multivariate adjustment, night shift work was related to statistically significant decreases of the total spine in T-scores of females aged ≥50 years. Furthermore, night shift work of the overall population (OR = 2.31 [95% CI, 1.03–5.18]; P = 0.043) and females aged ≥50 years (OR = 4.6 [95% CI, 1.21–17.54]; P = 0.025) was related to an increased prevalence of osteoporosis.
Night shift work correlates with a higher risk of osteoporosis in the population of the US adults, with the combined effect of age, gender, and harmful lifestyle.
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ReviewOsteoporosis in men

Summary

Introduction

Section snippets

Epidemiology

Mortality

Bone mass in men

Trabecular bone

Imaging osteoporosis in men

Fracture risk assessment in men

Causes of osteoporosis in men

Bone fragility associated with androgen deprivation therapy

General approach to the management of men with osteoporosis

Pharmacological therapy

Treatment in men receiving ADT

Treatment guidance for osteoporosis in men

Conclusion

Search strategy and selection criteria

Declaration of Interests

Bone

Bone

Bone

Bone

Bone

Trends Endocrinol Metab

Joint Bone Spine

J Bone Oncol

J Urol

J Urol

Bone

Bone

Lancet

Lancet Diabetes Endocrinol

Fragility fractures in Europe: burden, management and opportunities

Arch Osteoporos

Bone mineral density predicts osteoporotic fractures in elderly men: the MINOS study

Osteoporos Int

Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025

J Bone Miner Res

Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA)

Arch Osteoporos

Incidence of hip and other osteoporotic fractures in elderly men and women: Dubbo Osteoporosis Epidemiology Study

J Bone Miner Res

Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS)

J Bone Miner Res

Elderly men have much lower vertebral fracture risk than elderly women even at advanced age: the MrOS and MsOS (Hong Kong) year 14 follow-up radiology results

Arch Osteoporos

Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures

J Bone Miner Res

Meta-analysis: excess mortality after hip fracture among older women and men

Ann Intern Med

Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project

J Intern Med

Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women

JAMA

Hip fracture, mortality risk, and cause of death over two decades

Osteoporos Int

Potential mediators of the mortality reduction with zoledronic acid after hip fracture

J Bone Miner Res

Effect of osteoporosis treatment on mortality: a meta-analysis

J Clin Endocrinol Metab

Association between drug treatments for patients with osteoporosis and overall mortality rates: a meta-analysis

JAMA Intern Med

Peak bone mass

Osteoporos Int

Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats

J Orthop Res

Males have larger skeletal size and bone mass than females, despite comparable body size

J Bone Miner Res

Population-based study of age and sex differences in bone volumetric density, size, geometry, and structure at different skeletal sites

J Bone Miner Res

Bone mineral accrual from 8 to 30 years of age: an estimation of peak bone mass

J Bone Miner Res

Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study

Osteoporos Int

A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men

J Bone Miner Res

Association between bone turnover rate and bone microarchitecture in men: the STRAMBO study

J Bone Miner Res

Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment

Review
Osteoporosis in men