Maintaining healthy bone should begin in childhood and carry on through life. While osteoporosis is preventable, often diagnosis comes too late. Individualised treatment can halt progression
Dr Mary Short, Director of Sexual and Reproductive Health, ICGP, Ireland
It is estimated that 300,000 people in Ireland have osteoporosis.1 It is a condition that is often overlooked and undertreated, in large part because it is often clinically silent before manifesting in the form of a fracture.
Osteoporosis is a systemic skeletal disease characterised by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility One-in-two women and one-in-four men over 50 sustain a fracture as a result of osteoporosis and 90% of hip fractures are due to the condition. As our population ages, it poses an increasingly serious health and economic problem.
Risk assessment
While a DXA scan is considered by some to be the gold diagnostic standard there are simple questionnaires that may be used, eg. SCORE (Simple Calculated Osteoporosis Risk Estimation – widely available online). This simple tool estimates fracture risk based on race, age, previous fracture (traumatic versus non-traumatic), a history of rheumatoid arthritis, and prior use of HRT. Scores are graded into no risk, moderate risk and high risk – the latter being a priority for a DXA scan and treatment.
Alternatively there is FRAX (Fracture Risk Assessment Tool: www.shef.ac.uk/frax) which is a more in-depth version of SCORE.2 It is worth noting that inflammatory arthritis, eg. rheumatoid arthritis, is a risk factor for osteoporosis while osteoarthritis is not.
Signs and symptoms
Osteoporosis generally does not become clinically apparent until a fracture occurs. Two-thirds of vertebral fractures are painless and may present as muscle spasm, often in the mid-thoracic region following a fall or some minor trauma.3
For those presenting with back pain, it is usually specific and identifiable in the mid-thoracic to lower thoracic or upper lumbar spine. Patients often prefer to remain in bed because of fear of exacerbating the pain and this may be misunderstood as depression.
Patients with acute vertebral compression fractures may have demonstrable pain and pinpoint tenderness over the involved vertebra. Kyphosis and subsequent loss of lordosis are a consequence of the chronicity of multiple fractures over time.
The role of the DXA scan
The WHO definition of osteoporosis based on bone mineral density applies to post-menopausal women and men aged 50 years or older.4 This diagnostic classification should not be applied to pre-menopausal women, men younger than 50 years, or children.
The DXA scan will establish the prevalence of osteoporosis, but should not be used as the sole determinant of treatment options. It is important to establish fracture risk either by the SCORE or FRAX tools, as the ultimate goal is to prevent fractures and reduce morbidity and mortality from fragility fractures.
Whereas the T-score is the patient’s bone density compared with the BMD of control subjects who are at their peak BMD, the Z-score reflects a bone density compared with that of patients matched for age and sex.
The WHO definitions of osteoporosis based on BMD measurements in white women are summarised in Table 1. For each standard deviation (SD) reduction in BMD, the relative fracture risk is increased 1.5-3 times.
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Who should have a DXA scan?
The 2015 International Society for Clinical Densitometry (ISCD) Official Positions5 recommend bone density testing in the following patients:
Perimenopausal women with risk factors, eg. previous low impact fracture, anorexia, etc
Post-menopausal women younger than age 65 with a risk factor for low bone mass
Women > 65 and men > 70
Men < 70 with a risk factor for low bone mass
Adults with a fragility fracture or condition or medications associated with low bone mass or loss
Anyone not receiving therapy in whom evidence of bone loss would lead to treatment.
According to a study funded by the National Institutes of Health,6 osteoporosis will develop in fewer than 10% of older, postmenopausal women during the following rescreening intervals:
Women with normal BMD or mild osteopaenia, approx. 15 years
Women with moderate osteopenia, approx. five years
Women with advanced osteopenia, approx. one year.
Diagnosis
A clinical diagnosis of osteoporosis may be made in a post-menopausal woman or in a man over age 50 years who is at an elevated risk for fracture, as indicated by any of the following:
T-score of -2.5 or less at the spine or hip as determined by dual-energy x-ray absorptiometry (DXA)
Low impact fracture
FRAX score with 10-year risk for hip fracture ≥ 3% or for major osteoporotic fracture ≥ 20% in a patient with osteopenia.
Biochemistry
The diagnosis of osteoporosis is often opportunistic. Women over the age of 50 years and men over the age 60 years should have routine blood tests including calcium and vitamin D and thyroid function tests, as inadequate vitamin D levels or untreated thyroid disease can predispose people to osteoporosis. Magnesium is very important in calcium homeostasis.
Dietary and lifestyle measures
Adequate calcium and vitamin D intake are important at any age, particularly as we lay down our bony mass in childhood. They are essential in the prevention and treatment of osteoporosis. Vitamin D is increasingly being recognised as a key element in overall bone health, calcium absorption, balance (eg. reduction in the risk of falls), and muscle performance.
Good dietary sources of calcium include dairy products, sardines, nuts, sunflower seeds, tofu and green vegetables. Good dietary sources of vitamin D include eggs, liver, butter, fatty fish, and fortified food such as milk and orange juice.
Prevention is better than cure so early advice on general lifestyle, such as increasing weight-bearing and muscle-strengthening exercise, as well as cutting down on alcohol, quitting smoking and ensuring optimum calcium and vitamin D intake is important.
Protective measures should be taken in patients who must take glucocorticoids for other medical conditions. These include using the minimum effective dose, discontinuing the drug as soon as possible, and supplementing with calcium and vitamin D.
Pharmacologic treatments
Osteoporosis cannot be completely reversed but for those with established osteoporosis, medical intervention can halt its progression. If secondary osteoporosis is present, treatment for the primary disorder should be provided.
Bisphosphonates, either alone or in conjunction with vitamin D, are the most commonly used agents for osteoporosis. They have been shown to increase spinal and hip mineral density in postmenopausal women.
Well-conducted controlled clinical trials indicate that alendronate reduces the rate of fracture at the spine, hip, and wrist by 50% in patients with osteoporosis.7,8,9
Other oral bisphosphonates include risedronate or risedronate delayed-release, given daily, weekly, or monthly. Risedronate reduced vertebral fractures by 41% and non-vertebral fractures by 39% over three years.
Ibandronate, another bisphosphonate, has not shown efficacy in non-vertebral fractures in clinical trials.
Zoledronic acid is the most potent bisphosphonate available. It is a once-yearly intravenous infusion approved for the treatment of osteoporosis in men, post-menopausal women, and in patients with glucocorticoid-induced osteoporosis. It increases BMD at the spine by 4.3-5.1% and the hip by 3.1-3.5%, as compared with placebo.
Over three years, it reduces the incidence of spinal fractures by 70%, hip fractures by 41%, and non-vertebral fractures by 25%. A similar effect on vertebral fractures has been shown in men.
Over time, bisphosphonate therapy decreases bone turnover. Some patients on long-term bisphosphonate therapy risk developing transverse stress fractures and treatment intervals have now been established to reduce these iatrogenic fractures and jaw necrosis.
Patients at high risk may be continued on bisphosphonates after five years; however, in some patients, especially those with a lower risk of fracture, bisphosphonate treatment may be stopped. Where osteoporosis is mild, a drug holiday after four to five years of bisphosphonate treatment should be considered; if fracture risk is high, a drug holiday of one to two years may be considered after 10 years of treatment.
BMD and bone turnover markers should be monitored during the drug holiday, and treatment should be restarted if density declines substantially, bone turnover markers increase, or a fracture occurs.
Selective oestrogen receptor modulators (SERMs) are considered to provide the beneficial effects of oestrogen without the potentially adverse outcomes. Raloxifene is a SERM indicated for the treatment and prevention of osteoporosis in post-menopausal women. It has been shown to prevent bone loss, and data shows a 35% reduction in the risk of vertebral fractures in women and that it reduces the prevalence of invasive breast cancer, but it has been shown to increase the incidence of deep vein thrombosis, stroke, and hot flushes.10
Raloxifene has the added benefit of a reduced incidence of invasive oestrogen receptor-positive breast cancer, both during treatment and for at least five years after completion. This benefit of treatment should be taken into account when counselling patients.
The more minor adverse events (hot flushes, leg cramps) tend to be worse in the first six months of administration. Therefore, it is common practice to encourage perseverance with the drug during the first few months of treatment.
Raloxifene may be most useful in younger postmenopausal women without severe osteoporosis.
Denosumab is a humanised monoclonal antibody. It decreases bone resorption by inhibiting osteoclast activity. It is suitable for patients with comorbidities such as autoimmune disease or renal insufficiency. In postmenopausal women with osteoporosis, denosumab reduces the incidence of vertebral, non-vertebral and hip fractures.11 There is no requirement to discontinue denosumab at any stage due to its mode of action.
It also increases bone mass in men at high risk for fracture who are receiving androgen deprivation therapy for non-metastatic prostate cancer, and in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer.
Denosumab improved BMD significantly more than bisphosphonate treatment at the lumbar spine/total hip at 12-24 months. Strontium ranelate reduces the risk of both spine and non-vertebral fractures.12
The European Medicines Agency recommends the use of strontium ranelate for the treatment of severe osteoporosis in postmenopausal women and in adult men at high risk of fracture, for whom treatment with other medicinal products approved for the treatment of osteoporosis is not possible due to, for example, contraindications or intolerance. In postmenopausal women, strontium ranelate reduces the risk of vertebral and hip fractures.13
It should not be offered to those with severe renal impairment (creatinine < 30ml/min), immobility or other risk factors for DVT are contraindications.
Women, osteoporosis and HRT
In a paper published in the Journal of Clinical Endocrinology and Metabolism, March 2019,14 HRT or tibolone is recommended in those women with vasomotor symptoms where bisphosphonates or denosumab are not appropriate
This cohort of women should be under 60 years of age or within 10 years of the menopause.
They should fulfil the criteria of low risk of DVT; without prior myocardial infarction or stroke or high risk for cardiovascular disease; without breast cancer; willing to take tibolone or HRT.
There should be no additional contraindications to HRT. See also Figure 1 for recommended drug holidays for postmenopausal women.
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Conclusion
While osteoporosis is for the most part a preventable condition, often the diagnosis comes too late. The key to establishing and maintaining healthy bone starts in childhood. A diet rich in calcium and vitamin D and plenty of weight-bearing exercises are of paramount importance.
Posture mobility and flexibility play an important role as people age. Tai chi, yoga and pilates all contribute to improved bone health, better posture and improved proprioception, thus reducing falls and fractures. Walking stimulates bone formation and is considered better than cycling or swimming due to the weightbearing nature of the exercise.
There are some conditions that predispose to osteoporosis. Together, with or without an established risk, these are worthy of a DXA scan. Finally, while medications improve bone strength and bone health – osteoporosis is not reversible and medications should be chosen with the individual patient in mind.
References
Bone health and osteoporosis unit St James’s Hospital Dublin. https://misa.ie/clinical-services/bone-health-osteoporosis-unit/
World Health Organization Fracture Risk Assessment Tool. Available at www.shef.ac.uk/FRAX/
National Osteoporosis Foundation. www.nof.org/
WHO Criteria for diagnosis of osteoporosis. www.4bonehealth.org/education/world-health-organization-criteria-diagnosis-osteoporosis/
Adult Offiical Positions of the International Society for Clinical Densitometry. Indications for bone mineral density testing. www.iscd.org/official-positions/2015-iscd-official-positions-adult/
www.bones.nih.gov/
Geusens P. Bisphosphonates for postmenopausal osteoporosis: determining duration of treatment. Curr Osteoporos Rep. 2009 Mar. 7(1):12-7
Adler RA et al. Managing osteoporosis in patients on long-term bisphosphonate treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016 Jan. 31 (1):16-35.
Qaseem A, Forciea MA, McLean RM, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: A Clinical Practice Guideline Update from the American College of Physicians. Ann Intern Med. 9 May 2017
Lyu H et al. Comparison of denosumab and bisphosphonates in patients with osteoporosis: A meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2019 May 1. 104 (5):1753-1765
Querido W et all. The effects of strontium on bone mineral: A review on current knowledge and microanalytical approaches. Micron. 2016 Jan;80:122-34. doi: 10.1016/j.micron.2015.10.006. Epub 2015 Oct 20
Protelos summary of product characteristics. www.ema.europa.eu/en/documents/product-information/protelos-epar-product-information_en.pdf
The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 5, May 2019, Pages 1595–1622, https://doi.org/10.1210/jc.2019-00221
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