Osteoporosis

Osteoporosis is a progressive systemic skeletal disease characterised by reduced bone mass and microarchitectural deterioration of bone tissue, leading to increased bone fragility and susceptibility to fracture.
It may also be defined in terms of standard deviation of bone mineral density (BMD) from the young adult reference mean, the T Score.¹

It affects:

• 1 in 3 women aged >50 years
• 1 in 12 men aged >50 years.

This results in 310,000 fractures per year in the UK at a cost of £1.7 billion. The equivalent of employing 108,000 nurses or 34,000 GP's!This is expected to increase to £2.1 billion by 2010. This equates to an osteoporotic fracture every 2-3 minutes and is calculated to double in the next 50 years.^1,2

Risk factors

Some risk factors vary in importance according to the age of the patient:

• Corticosteroid therapy
  • Patients on corticosteroid therapy are at increased risk of fracture compared to patients not on steroids with the same BMD (T score).³
  • Any patient aged >65, or who has suffered a relevant previous fracture, taking any dose of steroid for >3 months, should be considered for prophylaxis/treatment, without BMD measurement.
  • Any patient <65 years should have BMD measured.
  • If the T score is <1.5 treatment should be considered.
  • Also consider BMD measurement in patients taking recurrent, intermittent courses of steroids as there is evidence to suggest that total cumulative dose is as important as chronicity for reducing BMD.
• Primary hypogonadism (men and women)
• Premature menopause (<45 yrs)
• Maternal history of hip fracture
• Chronic disorders associated with osteoporosis e.g. rheumatoid arthritis
• Female gender
• Aged>60
• Family history osteoporosis
• Prolonged secondary amenorrhoea
• Low body mass (<19 kg/m2)
• Smoking
• Poor diet (particularly if calcium deficient)
• Sedentary lifestyle
• Caucasian or Asian origin
• Anorexia nervosa
• Malabsorption syndromes eg coeliac disease
• Primary hyperparathyroidism
• Post transplantation
• Chronic renal failure
• Hyperthyroidism.
• Prolonged immobilisation
• Cushing's syndrome.

Unfortunately, the process that leads to established osteoporosis is asymptomatic and the condition usually presents only after bone fracture. Features differ according to the fracture site. The most common is deformity and loss of height due to vertebral collapse.⁵

Consider the following screening blood tests in patients suffering from osteoporosis to identify treatable underlying causes:

• FBC & ESR.
• U&E, LFT, TFT, Serum Ca., Alk. Phos.
• Testosterone/gonadotrophins in men.

Diagnosis of osteoporosis centres on the assessment of BMD:^6,7

• Single and dual X-ray absorptiometry (DXA)/Digital X-ray radiogrammetry (DXR) Assessment of mineral content of the entire skeleton and particularly at specific, vulnerable sites.
• DXA is regarded as the gold standard technique for diagnosis; the accuracy of DXA at hip exceeds 90% . Residual errors arise for various reasons. Incorrect diagnosis of osteoporosis can be caused by osteomalacia, osteoarthritis or soft tissue calcification.⁶
• DXR is a relatively new technique which is much simpler and less time-consuming than DXA. It can be carried out anywhere where there is the facility to perform a standard radiograph of the hand. It appears to have similar precision and accuracy to DXA in terms of diagnosing osteoporosis.⁸ It is a useful screening tool for osteoporosis following Colle's/other forearm fractures, without the need for additional radiographs. (This is a cohort of patients ripe for screening who often 'slip through the net').⁹ DXR seems to be slightly less sensitive than DXA in detecting osteoporosis.¹⁰

Other modalities used include ultrasonic measurement of bone. This can be used for the assessment of fracture risk, or selection of those in need of DXA/DXR. It is unreliable for diagnosis of osteoporosis and is associated with underdiagnosis. Radiography is useful for selection of patients in need of screening/formal diagnosis.

Bone density values in individuals can be expressed in relation to a reference population in standard deviation (SD); when SDs are used in relation to the young healthy population, this measurement is referred to as the T score.⁶

Risk of hip fractures is similar in men and women for any given BMD, so similar cut-off value for hip BMD can be used (<2.5 SD or more, T score<= 2.5, obviously using different reference value for different population).⁶

Performed by DXA and quantitative ultrasound.
Risk of fracture in elderly women roughly doubles for each SD reduction in BMD measured by DXA.
Biochemical assessment of fracture risk using bone turnover markers.
At the moment these are largely used as a research tool. Results of prospective studies suggests that their use combined with BMD measurement and clinical factors could improve fracture prediction in postmenopausal women.⁶

Consider hip protectors.
Ensure adequate calcium (0.5-1g) and Vit D (800iu) intake. Vitamin D is required for calcium metabolism and may reduce the tendency to falling.
Reduce polypharmacy, especially sedatives.

• Bisphosphonates are the mainstay of treatment for osteoporosis. They are however poorly absorbed and need to be taken separately from food. They may cause oesophageal irritation and should be taken sitting up with plenty of water. Etidronate was the first but has been superceded by the more powerful alendronate and risedronate both of which can be taken daily or weekly and the newer ibandronate that can be taken monthly. Less frequent dosing may improve adherence to therapy. All bisphosphonate trials have been controlled for Ca ² /Vitamin D and so bisphosphonates should usually have Ca ² /Vitamin D co-prescribed. Bisphosphonates act by inhibiting the action of osteoclasts.
  They have been shown to be cost-effective in European studies.^11,12
• Strontium ranelate has been licensed for the prevention of osteoporotic fractures in post-menopausal women with osteoporosis. This is the first drug in a new class of Dual Action Bone Agents (DABA). In addition to decreasing bone resorption by inhibiting osteoclast differentiation and activity, bone formation is increased by stimulation of pre-osteoblast replication leading to an increase in bone matrix synthesis.
• Raloxifene, a Selective Oestrogen Receptor Modulator (SERM) reduces postmenopausal bone loss and reduces vertebral fractures, but like HRT, may increase the risk of venous thromboembolism. Unlike HRT however, it decreases the risk of breast cancer (oestrogen positive tumours) but may exacerbate hot flushes. The CSM has advised that HRT should not be considered first line therapy for long-term prevention of osteoporosis due to the increased risk of breast cancer and cardiovascular disease.
• Parathyroid hormone (teripeptide), stimulates new bone formation but should be limited to those with an extremely low BMD or multiple fractures and an unsatisfactory response to bisphosphonates.

Routine monitoring of treatment by DXA is not recommended. Biochemical markers of bone turnover are a research tool at present, but may become clinically useful for selecting patients for treatment (patients with higher bone turnover respond better to treatment) and for monitoring the effectiveness of therapy. Markers of bone production are produced by osteoblasts and breakdown markers are collagen degradation products.

* American College Sports Medicine Guidelines suggest 50, 2 footed jumps of 8 cm, three times a week.
Grade A Evidence is evidence from meta-analysis of randomised controlled trials (RCT's) or at least one RCT or one well designed controlled study without randomisation.
Grade B Evidence is from at least one other type of well designed quasi-experimental study or from well designed non-experimental descriptive study e.g. case controlled studies.¹

Clinical Knowledge Summaries recommend that those with a confirmed T score of 2.5 or less or >2 vertebral fractures (if no other cause of vertebral fracture is apparent) should be offered treatment.³ Their criteria for offering BMD measurement are:

• X-ray evidence of osteopenia or vertebral deformity
• Decrease in height
• Long-term oral steroid treatment (3 months or more)
• Menopause at <45 years
• History of amenorrhoea for >1 year
• Primary hypogonadism
• Chronic disorders associated with osteoporosis eg rheumatoid arthritis
• Hyperthyroidism
• Maternal family history of hip fracture
• Body mass index <19
• Quantitative ultrasound of the calcaneum, or peripheral DXA/DXR of the wrist or heel suggesting osteoporosis.

Once osteoporosis is established and causes a fracture there is considerable associated mortality and morbidity.

• Approximately 14,000 people die per year from osteoporosis (greater than carcinoma of ovary, uterus and cervix put together).
• The mortality of hip fracture in older patients is 20% at 3 months.
• Only 50% of survivors regain full independence after fracture.
• Survivors consult their GP approximately 9 extra times in the year following their fracture.
• Only 1 in 3 vertebral fractures are diagnosed.
• One vertebral fracture increases a patient's risk of sustaining another vertebral fracture 5-fold, 20% of these within a year.
• Patients who sustain a vertebral fracture consult their GP, on average, 14 extra times in the year following it.