Consultant physician Professor Juliet Compston answers practical questions raised by GP Dr Pam Brown on the options for managing osteoporosis
Consultant physician Professor Juliet Compston answers practical questions raised by GP Dr Pam Brown on the options for managing osteoporosis
1 Which patients are at highest risk of osteoporotic fracture?
Osteoporotic fractures are more common in women than men and their incidence increases with age. Elderly women are therefore most at risk, although the risk in elderly men is also high. It is estimated that one in two women and one in five men over the age of 50 years will sustain an osteoporotic fracture.
In addition to age and sex, there are other factors that increase the risk of osteoporotic fractures. A previous fragility fracture substantially increases the risk of subsequent fracture, independently of bone mineral density. Other risk factors include:
• glucocorticoid therapy• aromatase inhibitors and androgen deprivation therapy• low body mass index (BMI)• untreated premature menopause• a family history of hip fracture• tobacco smoking• alcohol excess• immobility.
Several endocrine diseases are associated with osteoporosis, including hyperthyroidism, Cushing's syndrome and hyperparathyroidism. Other medical conditions that are associated with increased fracture risk include rheumatoid arthritis, malabsorption, chronic obstructive pulmonary disease, cystic fibrosis and inflammatory bowel disease.
2 Which site on the DXA scan should be used for diagnosis, and how should we interpret the scan if hip and lumbar spine results suggest different management?
Measurements of bone mineral density at either spine or hip can be used for the diagnosis of osteoporosis. However ,with increasing age, spine measurements become less reliable because of the presence of osteophytes, vascular calcification, vertebral fracture and spinal deformity, all of which may falsely increase the bone mineral density. Many experts believe that a measurement at the hip is sufficient for diagnosis, but particularly in younger postmenopausal women this approach will miss some cases in which osteoporosis is present in the spine, but not in the hip.
It is not uncommon to see low bone mineral density at one site but not at another. Low bone mineral density at either the hip or spine is predictive of fracture at any site, so treatment should be initiated if osteoporosis is demonstrated either in the spine or hip.
3 What is the role of pDXA or ultrasound examination in assessing fracture risk?
The values generated by these techniques cannot be used in the same way as DXA-based bone mineral density values in the spine and hip to make a diagnosis of osteoporosis. However, low values obtained using either pDXA or ultrasound can be regarded as a risk factor for fracture and constitute an indication for DXA-based measurements of the hip and/or spine. Because a number of different pDXA and ultrasound devices are available, the value at which referral for central DXA varies somewhat between systems. More detail can be found in position statements developed by the National Osteoporosis Society (nos.org.uk).
4 Which patients on oral steroid therapy need repeat DXA scans and what interval is optimal?
According to the guidelines produced by the Royal College of Physicians, primary prevention with a bisphosphonate should be initiated in men and women over 65 and/or who have sustained a previous fragility fracture, who are committed to at least three months of continuous oral glucocorticoid therapy. In such patients bone mineral density before therapy is not required, the priority being to start bone protective therapy as soon as possible. However, when and if glucocorticoid therapy is stopped, it is useful to obtain a bone mineral density measurement to assess whether continuation of treatment is indicated.
In other patients receiving glucocorticoids, who do not satisfy the criteria for primary prevention, bone mineral density should be performed to assess the need for bisphosphonate therapy. If the T-score is -1.5 or lower, treatment should be considered bearing in mind factors such as the dose of prednisolone and the presence of other risk factors. In these patients and those with T-scores above this threshold, the need for repeat DXA scans varies according to the clinical circumstances. In those with active disease requiring high doses of prednisolone, it is advisable to measure bone density at 12-18 monthly intervals (depending on the initial bone density values and the presence or absence of other risk factors). In those on low doses of prednisolone and low disease activity intervals of two to five years may be appropriate.
5 Should all patients have serum calcium measured before starting high dose calcium and vitamin D supplements?
Because calcium supplements are contraindicated in patients with conditions associated with hypercalcaemia and hypercalciuria, one view would be that serum calcium (and perhaps also urinary calcium) should always be checked before starting therapy with calcium and vitamin D supplements. However, in the absence of a clinical history suggestive of hypercalcaemia or hypercalciuria, calcium supplements in the doses usually provided (1-1.2g daily) are very unlikely to cause problems.
Since primary hyperparathyroidism is relatively common in older women, it is likely that some cases of mild hypercalcaemia will be missed if routine screening before therapy is not performed but there is little evidence that such patients are harmed by the doses of calcium given.
6 How should we manage a postmenopausal woman with osteopenia and two fractures?
Assuming that these are low trauma fractures, the woman should be treated in the same way as women who have osteoporosis (T-score =2.5). It is now well recognised that many fragility fractures occur in women who have osteopenia rather than osteoporosis as defined by their bone density. In such women, there are often factors that are partially independent of bone mineral density that are contributing to fracture risk, for example rheumatoid arthritis, glucocorticoids, smoking, or a family history of hip fracture.
Most of the available evidence supports the contention that women with osteopenia and fracture respond similarly to pharmacological intervention to those with osteoporosis, particularly when they have already sustained fractures. Since a previous fracture is an independent risk factor for further fracture, treatment should be initiated promptly and, where appropriate and possible, risk factors modified.Finally, although it is not unexpected that fragility fractures will occur in women with osteopenia, it is important to exclude other causes of fracture in such cases, particularly malignancy.
7 What investigations should be carried out to exclude secondary osteoporosis before initiating treatment in a woman with vertebral fracture?
A full history and examination should be performed. Routine tests include FBC, ESR, U&E, serum creatinine, serum calcium, phosphate and alkaline phosphatase, LFTs and thyroid function tests. Myeloma should be excluded by examination of serum for paraproteins and urine for Bence-Jones proteins. Tests for coeliac disease should also be considered.
Depending on the clinical circumstances other tests may be indicated. If serum calcium is increased, the serum parathyroid hormone level should be measured. In premenopausal women, serum oestradiol, gonadotrophin and prolactin levels may be helpful. Isotope bone scanning is indicated if there is suspicion of malignancy.Finally, unless there is a clear history of other fragility fractures, bone mineral density should be measured using DXA.
8 Which patients are not suitable for bisphosphonate therapy?
If there is a history of significant oesophageal disease, for example stricture or achalasia, bisphosphonates should not be prescribed. With other upper gastrointestinal disorders, for example dyspepsia, gastritis, duodenitis or ulcers, they should be used with caution and only when those disorders have been treated. Pregnancy is also a contraindication to bisphosphonate therapy.
In patients who develop upper gastrointestinal symptoms after taking bisphosphonates despite adhering strictly to the dosing regimen, withdrawal of treatment should be considered, depending on the severity of symptoms. Because upper gastrointestinal symptoms are so common in the elderly, the emergence of such symptoms during bisphosphonate therapy does not always imply a causal relationship. However, if symptoms persist and appear to be related temporally to taking the tablet, alternative bone-protective medication should be considered. Because it is very important that the dosing instructions for oral bisphosphonates are closely followed, oral bisphosphonates should not be prescribed to individuals with cognitive dysfunction or to those who may not be able to remain upright for 30 minutes after taking the tablet.
9 What influences adherence/persistence with therapy, and how can we optimise this?
This is an important question, since we know that approximately one half of patients prescribed treatment for osteoporosis have stopped treatment by one year. The factors responsible for poor adherence and persistence with therapy for osteoporosis (and other chronic diseases) are incompletely understood but there is some evidence that patient education may be helpful. Since treatment is long term and does not produce symptomatic improvement (and may cause side-effects), careful explanation of the aims of treatment, reassurance about its efficacy and reinforcement of the need to continue treatment for some years is appropriate.
In one study, nurse monitoring at three months after initiation of treatment was shown to improve adherence. Since most individuals who fail to adhere to treatment do so within the first few months of starting, early monitoring with the opportunity to discuss treatment issues with a health professional seems appropriate. There is no strong evidence that monitoring treatment by bone density measurements or biochemical markers improves adherence and persistence.Decreased dosing frequency may improve adherence and persistence. Reported levels of adherence and persistence with once-weekly bisphosphonates have generally been higher than with once-daily bisphosphonates, and once-monthly regimens are claimed to be better in this respect than once-weekly.
10 How long should patients continue with therapy?
The honest answer to this question is that we do not know! Most of the drugs used to prevent osteoporotic fracture have been tested in clinical trials for at least three years, in some cases five years, and fracture reduction is maintained throughout these periods. In most cases, therefore, five years is regarded as the minimum duration of therapy.
The decision whether to continue or stop treatment after five years can then be made of the basis of current bone mineral density values, fracture occurrence over the past five years and the presence of other risk factors. However, there are no hard and fast rules based on evidence to guide this decision and since bone loss and increased bone turnover resume in the first year or two after treatment is stopped, the patient may be exposed to increased fracture risk. On the other hand, there are some concerns about the adverse effects of prolonged suppression of bone turnover on bone strength, so the decision is complex.
11 Should all men with low trauma fracture be referred for expert assessment?
Many cases of osteoporosis in men can be managed in primary care. Expert assessment should be requested in younger men, and in those with no apparent risk factors for osteoporosis. Secondary causes of osteoporosis are more common in men than in women and should be carefully sought and treated if appropriate. Bone density measurement is often indicated to confirm the diagnosis, although is not necessary in older men with a history of fragility fractures and in whom risk factors are present.
12 What is the risk of osteonecrosis of the jaw in patients taking oral bisphosphonates for osteoporosis rather than intravenous bisphosphonates for malignancy? What advice should we give our patients?
The risk of osteonecrosis of the jaw in patients taking oral bisphosphonates for osteoporosis is extremely low – most cases have occurred in patients undergoing high dose intravenous bisphosphonate therapy for malignant disease. To date, approximately 180 cases have been described in patients taking oral alendronate, risedronate or ibandronate (the majority were taking alendronate) and the estimated incidence is 0.7 cases per 100,000 person-years' exposure.
Earlier this year the Medicine and Healthcare Products Regulatory Authority (MHRA) issued advice on this issue. Dental examination and treatment, if appropriate, should be considered before starting bisphosphonate therapy in patients with poor oral hygiene, cancer, chemotherapy or glucocorticoid therapy. And while on treatment, such patients should avoid invasive dental procedures if possible. There is no evidence that withdrawal of bisphosphonate therapy in patients requiring dental procedures reduces the risk of osteonecrosis of the jaw, and the management of patients should be based on an individual risk/benefit assessment.
13 Is nasal calcitonin useful in the management of severe pain from acute vertebral fracture?
There is some evidence that calcitonin is beneficial in the management of severe pain after acute vertebral fracture, although this has mostly been obtained using parenteral rather than nasal calcitonin.
Juliet Compston is honorary consultant physician at Addenbrooke's Hospital, and professor of bone medicine at the University of Cambridge
Competing interests None declared
• Bone mineral density can be measured in the hip or spine but spine measurements become less reliable with age and hip values alone may miss early osteoporosis only present in the spine
• Bisphosphonates should be started without DXA scan in anyone over 65 who will have at least three months of continuous oral steroids
• If there is no history suggesting raised calcium, calcium supplements at the usual doses are unlikely to cause problems
• Fractures may occur in osteopenia; if there is a previous fragility fracture they should be treated
• Five years is the minimum duration of therapy; current BMD, fracture in the past five years and other risk factors determine whether to continue
• The risk of osteonecrosis of the jaw in those taking oral bisphosphonates is very low
Risk factors for osteoporosis Bone mineral density independent
• Age• Previous fragility fracture• Maternal history of fracture• Oral glucocorticoid therapy• Current thinking• Alcohol intake =3 units/day• Rheumatoid arthritis• BMI =19 kg/m2• Falls
Bone mineral density dependent
• Untreated hypogonadism • Malabsorption • Endocrine disease • Chronic renal disease • Chronic liver disease •COPD • Immobility • Drugs, such as aromatase inhibitors and androgen deprivation therapy
what i will do now
Dr Brown responds to the answers to her questions
• We will continue to prioritise the management of those with previous fractures, those committed to oral glucocorticoids for three months or more, and frail elderly fallers
• I will now take more notice of low lumbar spine T-scores rather than concentrating on hip scores alone at diagnosis, while still using lumbar spine measurements when monitoring
• I hadn't previously thought of using DXA scanning at cessation of steroid therapy to decide whether to continue bone-sparing therapy in high-risk glucocorticoid users
• Considering both bone mineral density score and steroid dose when deciding on how soon to repeat DXA scans in those not yet needing drug treatment to prevent glucocorticoid-induced osteoporosis is useful
• It is reassuring to know that we do not have to measure calcium levels in all patients before starting calcium and vitamin D supplements
• We already see patients around three months after therapy initiation to check tolerability but eagerly await local availability of bone markers as an additional aid to compliance/persistence
Dr Pam Brown is a GP in Swansea and a clinical assistant in osteoporosis at Singleton Hospital