Bone health during the menopause: assessment and fracture prevention

One in five women over the age of 50 years have osteoporosis, and over half of the remainder have osteopenia.¹ From the age of 50 years, 40% of women will experience an osteoporotic fracture, and 15% will experience a hip fracture.^2-4 These fractures lead to pain and loss of mobility, confidence and independence. Following a hip fracture, arguably the most serious consequence of osteoporosis, 20% of people die within 12 months, 20% do not return to their private home (if living independently before the fracture) and only 35% return to their prefracture mobility level by 120 days.⁵

Pathophysiology

Oestrogen has protective effects on bone. It acts on osteocytes leading to decreased apoptosis and regulation of osteocyte-mediated bone remodelling (the coupling of bone resorption to bone formation). Oestrogen also acts on osteoclasts to reduce bone resorption, acts on osteoblasts to promote bone formation, and lowers renal calcium excretion (Figure 1Figure 1.).^6,7 In women, bone accrual occurs during childhood and adolescence, with peak bone mass attained during the third to fourth decade of life, followed by a plateau.⁸ Bone mineral density (BMD) declines from the perimenopause (where cycle length and menstrual loss begin to vary), with accelerated BMD loss of about 2.5% per year for the first two years postmenopause and then 1% per year for the next three years.^9,10 Hence, the most rapid bone loss occurs from one to two years before to two years following the final menstrual period (Figures 2a and bFigures 2a and b.).¹⁰

Menopause and its effect on bone loss

Although all women have a decline in BMD during the menopause, the difficulty in management is predicting who will develop osteoporosis and who will fracture. Most fractures in postmenopausal women occur in those who have osteopenia, as defined by dual energy x-ray absorptiometry (DXA) based on T-scores.¹¹ More rapid menopausal bone loss at the spine and a lower baseline lumbar spine BMD at the time of the final menstrual period are associated with a greater risk of fracture.¹² However, other predictive factors are less clear. During the perimenopause, low body weight is associated with a greater risk of future osteoporosis and an elevated body mass index is associated with less perimenopausal bone loss; however, fracture rates are similar across body mass index categories.^13,14 Women of Asian ethnicity may also have greater bone loss during menopause; however, many studies show their fracture risk is lower than women of European ancestry.^10,15

Diagnosis, screening and investigation

DXA is currently the gold standard for the diagnosis of osteoporosis, with osteoporosis defined as a T-score at the lumbar spine, femoral neck, total hip or mid radius of –2.5 or less, and osteopenia defined as a T-score of more than –2.5 and less than –1.0.¹⁶ These values relate to postmenopausal women. In practice, osteoporosis should also be diagnosed if there has been a fragility fracture due to minimal trauma (occurring from standing height or less) or there is radiological presence of a vertebral compression fracture (>20% loss of height) without a history of trauma regardless of the T-score.^17,18 Nevertheless, in the setting of a known fracture, DXA may be helpful to stratify risk and monitor treatment response but is not essential before initiating specific treatment.

DXA is reimbursed under the Medicare Benefits Schedule (MBS) for people aged 70 years or more, for those with a history of fragility fracture and in those with medical conditions known to decrease BMD (e.g. malabsorptive conditions, chronic kidney or liver diseases, rheumatoid arthritis, thyroxine excess, hyperparathyroidism, hypogonadism or prolonged glucocorticoids).¹⁹ In addition to these MBS indications, 2023 Australian menopause guidelines also suggest DXA should be considered in women with normal or low body weight, limited mobility, poor overall health, malnutrition, diabetes mellitus, previous tissue transplant, HIV infection, those who are current smokers and those consuming more than two standard drinks of alcohol per day.²⁰ These indications are not reimbursed under the MBS and so would incur a cost to the patient (from about $105).

In the absence of DXA, readily available online screening tools such as the Fracture Risk Assessment Tool (FRAX; https://frax.shef.ac.uk/FRAX/tool.aspx) and Garvan Fracture Risk Calculator (https://fractureriskcalculator.com.au/calculator/) can provide an estimate of the risk for fracture over the next five to 10 years. However, these tools do not predict osteoporosis development at the time of menopause because they do not take into account the rapid BMD decline that occurs around the final menstrual period. Few studies have examined the use of FRAX in women during perimenopause, and fracture prediction in these women may be less accurate than for older women.²¹

Additional investigations may be required in women diagnosed with osteoporosis. Vitamin D levels should be checked in high-risk women and measurement of renal function and calcium levels are important in treatment selection. Investigations for secondary causes of osteoporosis can be performed if there is clinical suspicion (Box 1Box 1. and Box 2Box 2.).¹⁸ Thoraco-lumbar spine x-ray may be performed if vertebral fractures are suspected (kyphosis or ≥3 cm loss of height).

Preventive measures recommended for all women

Conservative measures for preventing bone loss include smoking cessation, minimising alcohol intake (≤10 standard drinks per week and ≤4 standard drinks per day), and ensuring adequate calcium intake and serum vitamin D level. These measures are recommended for all women during the menopause because of their relative safety and the difficulty in predicting who will develop osteoporosis (Table 1Table 1.).^22-25 Australian guidelines recommend 1300 mg daily calcium intake for postmenopausal women, which equates to around three to four servings of dairy (or other calcium-rich food) daily.^18,26 Many Australians do not achieve the recommended daily intake, and Healthy Bones Australia (https://healthybones
australia.org.au/) provides factsheets on how this can be achieved, but if this is not possible with diet then a supplement can be considered.^27,28

A quarter of Australians are considered vitamin D insufficient (level <50 nmol/L).²⁹ The major source of vitamin D is via sunlight, with only small amounts in the diet. In general, Australians only need to spend a few minutes in sunlight daily over summer to achieve adequate vitamin D levels; however, in winter this may increase to two to three hours per day, and is affected by skin tone and body exposure.^28,30 If vitamin D levels are insufficient, vitamin D3 supplements should be started, which are safe and often continued life long.

High-intensity progressive resistance training can increase BMD in pre-, peri- and postmenopausal women, and also may protect against minimal-trauma fractures in postmenopausal women.^31-33 In addition, exercise programs and balance training can reduce falls and fall-related fractures.^34,35 Specific programs exist around Australia that are tailored for osteoporosis (e.g. Onero – https://onero.academy/osteoporosis-exercises/) and individual programs can also be designed by physiotherapists and excercise physiologists using the Healthy Bones Australia Exercise Prescription Guideline (https://healthybonesaustralia.org.au/wp-content/uploads/2024/02/hba-ex-presc-final-compressed.pdf).

Pharmacological treatment

Women with osteoporosis

Multiple international guidelines recommend using risk-stratification systems to predict the risk of future fractures, and hence the need for pharmacological treatment.^17,36,37 A recent fracture is a major risk factor for future fractures; one in 10 people will sustain another fracture within the first 12 months after an initial fracture, and the risk then decreases slowly over time.^38,39 In the presence of vertebral or hip fractures, pharmacological therapy is strongly advised. Treatment is also advised in women following other minimal trauma fractures with a T-score of –1.5 or below, and in the absence of a fracture with a T-score of –2.5 or below or a high FRAX score.¹⁸ Although some women may not meet PBS criteria for reimbursed antiresorptive agents, the cost of some antiresorptive agents approximates the PBS-reimbursed cost and hence should not be a barrier to warranted pharmacotherapy.

Choice of pharmacotherapy in women with osteoporosis should follow local osteoporosis guidelines.^18,40 Options for pharmacological treatment in women with osteoporosis are summarised in Table 2Table 2..

Women with osteopenia

In women during the perimenopause and early postmenopause who do not have osteoporosis, consideration may be given to use of menopausal hormone therapy (MHT) to prevent BMD decline, after discussion of the risks versus benefits of therapy. MHT improves BMD at the lumbar spine and to a lesser extent at the hip, and is associated with a 20 to 35% reduction in nonvertebral, vertebral and hip fractures, although the optimal dose for bone preservation is unclear.^41-43 In women who have other bothersome symptoms of menopause, MHT is a useful choice for both managing symptoms and providing bone protection. Although there is robust evidence for the use of MHT for bone protection in asymptomatic postmenopausal women with osteopenia, guidelines on who and when to treat have previously been lacking.⁴⁴ A study examining peripheral BMD in women aged 50 years or above found that those with a T-score of –1.8 or less had increased risk of fractures within the following 12 months.⁴⁵ Based on this evidence, recent Australian and International menopause guidelines have suggested MHT for asymptomatic women aged under 65 years with a T-score of –1.8 or less (and >–2.5) and a low FRAX risk score, and without contraindications to MHT, to prevent bone loss.²⁰

Alternative options to MHT include low-dose bisphosphonate therapy, which has been shown to improve BMD in early postmenopausal women.⁴⁶ However, there is a lack of evidence in women commencing treatment around the perimenopause, and this approach is not recommended by current guidelines. Importantly, denosumab is not an appropriate choice for preventive therapy because of the rapid loss of efficacy and rebound increase in bone resorption after cessation.

If or when MHT is stopped, BMD will decline rapidly, with similar rates and magnitude to natural menopause.⁴⁷ Some studies suggest that fracture incidence following cessation of MHT appears to increase to baseline. In the Women’s Health Initiative trials, rates of fracture following cessation of MHT approximated the placebo group; however, given the reduction in fracture during treatment with MHT, the cumulative fracture prevalence over 13 years was lower in women treated with combined oestrogen and progestogen.⁴⁸ Importantly, the women in these trials were not all commenced on MHT during the perimenopause, and limited data are available in this age group. A small study examined whether antiresorptive agents can prevent BMD decline after MHT cessation and found that 10 mg alendronate daily for 12 months prevented bone loss and instead led to a rise in BMD at all sites.⁴⁹ However, this approach has not been incorporated into clinical guidelines.

Monitoring on treatment

If any treatment is commenced, clinical review after three months is appropriate to assess tolerability. A repeat DXA is subsidised under the MBS 12 months after a treatment change or every one to two years depending on the indication. For women who have started treatment, minimal change is expected after 12 months of treatment, and therefore we suggest repeating a DXA only after 24 months in most women, unless there is a clinical suspicion of more rapid BMD change. In women not on treatment, with T-scores less than –2.5, or Z-scores less than 1.5, a repeat DXA is subsidised every two years; in other women, clinicians can consider a privately funded DXA scan to assess the magnitude of perimenopausal bone loss.

Serial DXA should be performed at the same practice, on the same machine to allow for comparison.⁵⁰ Any difference in BMD on serial DXA should be reported in regard to the least significant change of the machine and operator. If a DXA report states only the percentage change in BMD, with no reference to the significance of this change, or the least significant change of the machine, it is difficult to determine if there has been a true change in BMD or if the difference is simply due to machine variability. In these cases, however, 4 to 5 % in the lumbar spine and 5% elsewhere can be used as a rough estimate of significant change.

Conclusion

Menopause is associated with a significant, rapid decline in BMD, beginning before the final menstrual period. Given the burden of osteoporosis and fractures as women age, identifying women at higher risk, and implementing measures to reduce BMD decline, are vitally important. All women should be encouraged to stop smoking, reduce alcohol intake, optimise calcium intake, have normal vitamin D levels and exercise. Pharmacological options should be considered according to local guidelines, with osteoporosis treatment preferred in women with osteoporosis (fragility fracture and/or a T-score ≤–2.5), and MHT considered in those with T-scores of  –1.8 or less. ET

COMPETING INTERESTS: None.

ACKNOWLEDGEMENT: The authors would like to acknowledge Professor Susan Davis for reading an earlier version of this article and providing feedback.

References