Bone health 2022: an update

If one examines the epidemiology of osteoporosis and fragility fractures, it becomes understandable why the Board of the International Menopause Society decided to focus on bone health as its theme for 2021. On World Menopause Day, the annual White Paper of the Society was on the topic of bone health. This present issue of Climacteric further explores that theme in greater depth.

Worldwide, osteoporosis causes more than 8.9 million fractures annually, resulting in an osteoporotic fracture every 3 seconds [1]. It is estimated that osteoporosis affects 200 million women worldwide. One-tenth of women aged 60, one-fifth of women aged 70, two-fifths of women aged 80 and, actually two-thirds of women aged 90 carry this diagnosis [2]. Worldwide, one in three women after the age of 50 will experience osteoporotic fracture [3]. Bone as well as muscle is a hormonally sensitive organ. At menopause, the removal of estrogen has much greater effects in women than in men of similar age. The female-to-male ratio of osteoporotic fractures is approximately 1.6, such that 80% of forearm fractures, 75% of humerus fractures, 70% of hip fractures, and 58% of spine fractures occur in women [1]. A prior fracture is associated with an 86% increased risk of any subsequent fracture [4]. Fragility fractures are a leading cause of chronic disease morbidity. For instance, in Europe, fragility fractures are the fourth leading cause, after ischemic heart disease, dementia, and lung cancer; however, they surpass chronic obstructive pulmonary disease and ischemic stroke [5]. After sustaining a hip fracture, 10–20% of formerly community-dwelling patients require long-term nursing care [6]. Overall, hip fractures cause the most morbidity and reported mortality rates in up to 20–24% in the first year after a hip fracture [7]. Loss of function and independence among survivors is profound, with 40% unable to walk independently, and 60% requiring assistance a year later [8].

Contrast that with early detection of cancer. In localized breast cancer where there is no sign that the cancer has spread outside the breast, the 5-year survival according to the SEER (Surveillance, Epidemiology, and End Results) database in the US is 99% [9]! Even regional breast cancer, defined as spread outside the breast to nearby structures or lymph nodes, has an 86% 5-year survival. In developed countries where women have access to periodic competent breast screening by imaging techniques, for many the diagnosis of localized breast cancer and the psychological ramifications may actually exceed the physical manifestations. Contrast that with the statistics provided above concerning osteoporosis and fragility fracture and, hopefully, it becomes obvious why we, as representatives of the International Menopause Society, have chosen the topic of bone health for this extremely important special issue of Climacteric.

In this issue, Lorentzon et al. [10] further develop the details of this somber picture of the burden of disease resulting from the age-related increase in osteoporosis and related fractures. It is of interest to note that the age-standardized rate of hip fractures per 100,000 women varies across the globe, being highest in Scandinavian countries and lowest in Africa.

Fracture risk assessment of individuals without fracture was previously based on the individual assessment of known risk factors. In this issue, McCloskey et al. [11] describe how the FRAX® algorithm has facilitated the assessment of fracture risk on the basis of fracture probability over the next 10 years, using an internet tool that integrates validated risk factors for fracture with or without the use of bone mineral density (BMD). Country-specific FRAX models are now available for 73 countries based on national epidemiology of hip fracture and mortality rates.

Unfortunately, FRAX does not tell us when to treat. Chandran and Kwee [12] explain the difficulties in setting intervention thresholds (ITs). They should ideally be calculated for every country to reflect local epidemiology, cost and availability of medication to determine when it becomes appropriate to treat. Using a fixed IT such as the USA-values based on FRAX, may be totally inappropriate in a different country. A patient-centric approach should be adopted with individual concerns and preferences addressed.

Reid [13] emphasizes the importance of addressing a bone-friendly lifestyle and optimizing diet, calcium and vitamin D status before embarking on bone-specific medication. This involves cessation of smoking, limiting of alcohol intake to ≤ 2 drinks per day, regular moderate- to high-impact exercise, maintaining a body mass index of about 25 kg/m², a dietary protein intake of 1 g/kg/day, total dietary intake of calcium > 500 mg/day and vitamin D supplementation in those with a lack of exposure to sunlight or 25-hydroxyvitamin D levels < 30 nmol/l.

Menopausal hormone therapy (MHT) was first-line therapy in osteoporosis prevention and treatment until publication of the Women’s Health Initiative results in 2002. However, in spite of solid evidence of efficacy, poor understanding of the benefit/risk ratio has led to relegation of MHT to a second-line therapy. Jiang and Kagan [14] explain in great detail how we came to this situation and present more recent evidence as to how to bring back MHT as an option in osteoporosis management in a safe and scientifically based manner.

Non-hormonal medical therapy, apart from hormone therapy, plays a major part in our strategy of lowering the burden of osteoporosis-related fractures. Palacios [15] provides an overview of presently available therapeutic options, including efficacy, side-effects and indications. Goldstein [16] goes into detail about the various selective estrogen receptor modulators and the evidence of how each affects bone, especially in light of the variety of indications for each. Anabolic drugs, unlike the antiresorptive agents, have their own unique role in therapy for some individuals. McClung and Clark [17] address their use as well as some newer available options and recommendations.

Conradie and de Villiers [18] address premenopausal osteoporosis as a separate entity from postmenopausal osteoporosis. The diagnosis is not based on BMD alone and the World Health Organization classification does not apply. It is reserved for those with evidence of fragility and may also be considered in women with low bone mass and an ongoing secondary cause of osteoporosis. Optimal treatment of secondary causes of bone loss is essential. The safety of bone-specific therapy, especially long-term and during pregnancy, remains uncertain. Bone-specific treatment increases BMD in premenopausal women with osteoporosis, but there are no study data confirming short-term fracture prevention with use of these agents.

Breast cancer treatment often leads to estrogen deprivation with a subsequent increased risk of fracture. Stevens and Hellig [19] advise on remedial action with concomitant antiresorptive therapy. This may, in addition, function as adjuvant therapy in moderate- to high-risk breast cancer to prevent disease recurrence.

Vasanwala, Gani and Ang [20] describe how episodes related to intrauterine life, childhood and adolescence may affect peak bone density and bone health in later life. It is estimated that a 10% increase in peak bone mass will delay the onset of osteoporosis by 13 years in a woman.

Thus far we have focused on bone exclusively. However, increasing evidence shows that muscle strength and function may be as important a risk factor and, conversely, a protector when one looks at fragility fractures. Sarcopenia is defined as a syndrome characterized by progressive and generalized loss of muscle mass and strength [7]. This has been further refined to include muscle performance such that presarcopenia is low muscle mass without an impact on muscle strength or performance, while severe sarcopenia involves all three being deranged. Sarcopenia itself is low muscle mass with either low muscle strength or low physical performance but not both [21].

So, further in this issue Mandelli et al. [22] have an extremely interesting thesis regarding the role that estrogens exert, not only well known in bone, but also muscle development and maintenance. Finally, Laskou et al. [23] discuss the newer concept of osteosarcopenia, wherein the coexistence of both entities simultaneously may accelerate and increase the risk, morbidity, and even mortality from falls, fractures and disability.

As guest editors, we hope that you will not only enjoy this special issue on Bone health, but will implement the information described by our distinguished authors and make a difference in the lives of the patients we serve.

Source of funding

Nil.