In this study, we described the differences in the prevalence, DALY and mortality of LBMD between men and women in 2019 and the temporal trends from 1990 to 2019. Women showed higher SEV then men at the global level, as well as in most regions and countries, suggesting that osteoporosis is more likely to affect women than men. However, we found men demonstrated higher ASDR and ASMR than women, suggesting that osteoporosis related disease burden is heavier in men. Men and women also differed with each other in the causes of LBMD-related deaths and disabilities. Road injuries are more likely to be the cause of osteoporotic deaths and disabilities in men with LBMD, while fall-related osteoporotic deaths and disabilities were more common in women.
A number of factors have been identified to increase the risk of developing LBMD or osteoporosis. Uncontrollable risk factors for osteoporosis include advanced age, female sex, menopause, family history, and race, while controllable risk factors include low body weight, low sex hormones, smoking, excessive drinking, lack of physical activity, dietary calcium and vitamin D deficiency [1, 7, 8]. Among these risk factors, female sex is associated with a twice higher risk of developing osteoporosis. This increased risk in women is explained by the lack of estrogen after menopause. Women aged over 70 years old have experienced long-term deficiency of estrogen, and overactivated activated osteoclasts and enhanced resorptive function are the main cause for bone loss in the absence of estrogen, which leads to osteoporosis [9]. Besides, the rate of hyperparathyroidism in postmenopausal women is also higher, which leads to hypercalcemia and bone diseases[10, 11]. A third reason is that women tend to live significantly longer than men, and the absolute number of osteoporosis in older women reached six times as many as that of men due to the higher proportion of women of advanced age [12].
However, after standardizing by age, we found the DALY and mortality rates were higher in men than that in women at the global level and in most regions and countries. Unlike women, LBMD-related absolute DALYs in men mainly came from those aged 65 years or younger, and the number of DALYs decreased with age. Accordingly, higher rate of DALY in men than in women was seen only in people younger than 65 years of age. Suggesting that LBMD-related disabilities in men mainly came from those in young people. One of the main reasons lies in the differences of work and physical activities between men and women. Although the BMD in men of young age is higher than in the old, it should also be noted that young men are more likely to participate in many high energy work, sports, or activities, which render them at increased risk of fracturs on a condition of decreased BMD with age. For the causes of osteoporotic fractures, age standardized mortality and DALY rate caused by transport injuries were both higher in men than that in women, which could be attributed to the fact that men are more likely to participate in vehicle- and road-related work or activities, including driving, cycling, and motorcycle riding. Additionally, higher mortality and DALY rates were seen in middle to high SDI countries, which may also be due to better road transportation facilities and more popularized vehicle use. Compared to people with normal BMD, people with decreased BMD are more likely to suffer fractures from accidental events during these work or activities, especially vertebral or hip fractures, which are usually associated with disabilities and increased mortality rate [13, 14].
The difference of hormonal effects on bone mass may also explain the difference of prevalence and burden of PBMD between men and women. In women, the loss of bone mineral density is accelerated by the loss of protective effects of estrogen on bone quality in the postmenopausal decade. Estrogen and testosterone have the same effect on bone mass in older men[9, 10, 15]. Androgens can maintain BMD by directly binding to androgen receptors or indirectly binding to estrogen receptors through aromatization to estrogen, and testosterone deficiency during aging is an important factor for bone loss in men [16]. The level of testosterone begin to drop by 1–2% annually since the age of 40 years[17], earlier than the age of menopause in women. Such differences are also reflected by the different changes of BMD with age between women and men. The Canadian Multicenter Osteoporosis Study suggested that women's lumbar spine BMD peaked at ages of 33 to 40 years, while men's lumbar spine BMD peaks at ages of 19 to 33 years, much earlier than women, suggesting that bone density in men begins to decrease earlier than women [18]. This earlier decrease renders men at increased risk of developing LBMD and osteoporosis during a wider range of the whole lifespan.
Men and women have different unhealthy living habits, such as excessive drinking and smoking, which are lifestyle risk factors for osteoporosis[19, 20]. Besides, men also tend to have higher incidence rate of many chronic diseases that will affect BMD, such chronic obstructive disease (COPD) and diabetes [21]. Due to smoking and occupational exposure, the prevalence of COPD in men is consistently higher than that in women [22]. The prevalence of osteoporosis in COPD patients is significantly higher than that in healthy controls [23]. Also, the limitation of chest diastolic function in patients with osteoporosis will inhibit respiratory function and aggravate COPD[24], which in return decreases BMD. Hypoxic state [25], Vitamin D deficiency [26], and lack of activity are the main reasons to induce bone loss in patients with chronic COPD. Avoid related lifestyle risk factors for these chronic diseases and for osteoporosis will help to reduce the related burden in men.
Clinically, osteoporosis in men have been overlooked for too long [27]. More attention has been paid to the prevention and treatment of osteoporosis in postmenopausal women, while ignoring the disease in men [28]. For osteoporosis in women, menopause is a clear time point that inform clinicians to pay increased attention to BMD in women. When indicated, anti-osteoporotic therapies can be initiated to avoid bone loss. However, there are few studies or guidelines to help clinicians to determine when to perform osteoporosis screening in men, and when to initiate the treatment of osteoporosis to prevent osteoporotic fractures [7], which are associated with substantial disabilities and socioeconomic burden [2]. Existing guidelines suggest that men over 70 years of age should have dual-energy X-ray absorptiometry measurement, which is the gold standard for determining BMD and can be used to evaluate the efficacy of drug intervention [29, 30]. For men aged 50 to 69, BMD should be examined only if they have one or more of the following risk factors: disease history such as hypogonadism, delayed puberty, hyperthyroidism, hyperparathyroidism, rheumatoid arthritis or COPD; Drug use such as glucocorticoids or gonadotropin-releasing hormone agonist; and lifestyle risk factors such as excess alcohol drinking or smoking [31]. However, as the burden of osteoporosis is heavier in men, it remains to determine whether the screening of BMD in elderly men without risk factors should be advanced in old age to reduce the burden. The balance between health benefits and economic cost of early screening should also be taken into consideration in future studies.
This study has some limitations. Due to the well-established medical facilities and increased medical input, people in high-SDI countries are more likely to have regular screening for BMD, which helps to detect more osteoporosis cases, especially those with latent fractures. In low-income countries, patients tend to seek medical care and have BMD tested only after they experience adverse symptoms (back pain, herniated disc, difficulty walking). This results in potential bias when estimating the prevalence and burden of LBMD. In addition, GBD 2019 covers almost all the countries and territories in the world, and the determination of LBMD may be affected by the diagnostic standards, diagnostic equipment, and physician’s awareness of BMD screening; Thirdly, death certificate is used as one of the data sources. Although it is an important source of public health data, it may be misclassified because it is difficult to determine the potential cause of death [32].