Osteoporosis: strategies to minimise fracture risk

Osteoporotic fractures are common in both men and women over the age of 60 years.¹ These fractures significantly affect quality of life, morbidity and mortality for sufferers and their families, and increase the risk of future fractures.^1,2 Even though osteoporotic vertebral fractures may be asymptomatic, they are associated with an increased risk of subsequent fractures, including hip fracture.³

An Australian study has suggested that only 20% of patients receive osteoporosis treatment after sustaining a low-trauma fracture.⁴ General practitioners are ideally placed to diagnose and manage osteoporosis and close this therapeutic gap.

This therapeutic brief aims to promote optimal management of osteoporosis through early recognition of high risk patients, prompt diagnosis, and initiation of treatment where indicated. Consider a bone mineral density (BMD) test (by DEXA scan) for your veteran patients who may be at increased risk of osteoporosis, and for those aged over 50 years who have sustained a low-trauma fracture.

Recognise risk factors

Check BMD

Address modifiable factors

Consider osteoporosis treatment

Osteoporosis is defined by low bone mass and microarchitectural deterioration of bone leading to fragility and increase fracture risk after minimal trauma (i.e. a fall from a standing height or less). The WHO defines osteoporosis according to BMD, with a T-score of -2.5 or below considered diagnostic.⁵

Although most common in postmenopausal women, osteoporosis also occurs in men, in whom bone loss occurs later than in women.⁶ Secondary causes of osteoporosis are responsible for 30 – 60% of cases in men, and include hypogonadism, excessive alcohol intake and oral glucocorticoid use.⁶

Recognise risk factors

• Increasing age and menopause are the most common risk factors.
• Address secondary and reversible causes of osteoporosis, especially in men.
• The risk of bone loss is increased with some long-term treatments including oral glucocorticoids and some anticonvulsants (phenytoin, barbiturates).^7,8 In addition, the risk of falls and fractures is increased by some medicines (psychotropics, sedatives) and by polypharmacy, especially in older people.⁹

Table 1: Risk factors for osteoporotic fractures and the most important indicators for BMD testing (adapted from NPS News #53 August 2007)¹⁰

Major risk factors

Advanced agea,b

Low BMD

Female

Early menopause (<45 years)b

Amenorrhoea (>6-12 months)

Primary hypogonadismb

Previous low-trauma fracturea,b

Family history of low-trauma fracturea,b

Low body weighta,b

Oral glucocorticoid therapya,b

Increased propensity for fallsa,b

Cigarette smokinga

Other risk factors

Asian or Caucasian

Regular excessive alcohola

Sedentary lifestyle/prolonged immobilisation

Inadequate calcium

Vitamin D deficiency

High bone turnovera

Other secondary causes of osteoporosisc

^a At least partly independent of BMD

^b Important risk factors that indicate the need for BMD testing in men and/or women

^c e.g. Rheumatoid arthritis, malabsorption syndromes, primary hyperparathyroidism, clinical hyperthyroidism chronic renal/hepatic failure, long-term use of some anticonvulsant therapy

Check BMD

• BMD is useful in predicting fracture risk and helps guide decisions regarding treatment choices.
• BMD testing should only be done if the result will influence management.¹⁰
• Medicare rebate for DEXA scanning is now available for all men and women aged 70 years and over.
• For most patients, it is not necessary to repeat BMD testing prior to two years.¹¹

Although fracture risk increases at lower BMD, the risk of fracture is not solely determined by BMD. Other factors unrelated to bone mass loss come into play, including falls, high alcohol intake and visual impairment.¹³ Importantly, for any given BMD, fracture risk is much greater in the elderly than in the young.¹⁴

If bone loss occurs while on treatment, poor compliance and/or other contributing factors or underlying secondary causes should be considered.

Address modifiable factors

As not all risk factors for fracture are dependent on BMD (table 1), specific drug therapy for osteoporosis may not fully modify fracture risk. It is thus important to address other modifiable risk factors which may help maintain BMD and reduce fracture risk, by:

• Ensuring adequate calcium intake – 1300 mg, or 4 serves of dairy food daily equivalent to one litre of milk.¹⁵ In practice a supplement is often required.
• Avoiding vitamin D deficiency. Exposing the hands, face and arms to direct sunlight for 5-15 minutes 4-6 times a week can prevent this, although recommended exposure times vary with skin colour, latitude and season.¹⁶ In practice, a supplement is often required.
• Encouraging low impact exercise which improves strength and balance (e.g. Tai Chi).¹⁷
• Avoiding excessive alcohol intake.⁶
• Reviewing medication regimens to address drug therapy that may contribute to falls and fracture risk. Consider referral for a Home Medicines Review (HMR).

Vitamin D deficiency

Vitamin D deficiency is relatively common in certain groups, such as the elderly, people with dark skin (especially those who dress modestly for cultural or religious reasons) and those with chronic illness.¹⁵ Elderly Australians in residential care are at increased risk of vitamin D deficiency, with estimates ranging from 45 - 86%.^18-20

• Vitamin D deficiency can lead to bone pain, muscle weakness, increased risk of osteoporosis, falls and fractures.^21,22
• Most people are unable to meet the recommended daily intake for vitamin D from dietary sources alone, and vitamin D is primarily obtained from sun exposure.¹⁶

In high risk individuals routine supplementation is likely to be more cost-effective than a ‘test and treat’ approach.

Patients with moderate to severe vitamin D deficiency (25-OH vitamin D 25 nmol/I or below) may require higher doses (3000 – 5000 units daily for 6 to 12 weeks) than those used for routine supplementation (approximately 1000 units daily).¹⁶

In Australia, vitamin D is available as a supplement as either ergocalciferol (D2) or cholecalciferol (D3). Vitamin D3 appears to be more effective than D2 in raising serum 25-OH vitamin D levels.²³ Although cod liver and halibut oil capsules contain cholecalciferol, they also contain vitamin A which can be toxic at high doses.

Consider specific osteoporosis treatment

• Ensure adequate calcium and vitamin D (supplements are often necessary).
• In older patients with prior fractures, alendronate or risedronate should be considered first.
• Strontium ranelate and raloxifene offer an alternative to bisphosphonates.¹⁷
• In patients taking oral glucocorticoids (>7.5mg/day of prednisolone or equivalent for more than 3 months), consider risedronate as prophylaxis against bone loss (RPBS listed).²⁴

Current pharmacological therapies for osteoporosis target the mechanism of the disease. Bisphosphonates and raloxifene inhibit bone resorption (antiresorptives). Strontium ranelate appears to have a dual mode of action, decreasing resorption and increasing bone formation.²⁴

The decision to treat should take into account the patient’s age, T-score and fracture history.

Choice of agent

The choice of agent will be determined by the patient’s gender, menopausal status, age, medical history, and patient preference for certain regimens. There are few head to head trials of active agents. Studies have generally been active agent against placebo and conclusions cannot be made across these trials regarding their relative efficacies.

Primary fracture prevention

Alendronate and risedronate are now available on the PBS (for use as a sole antiresorptive agent) for osteoporosis in women and men aged 70 years or older with a T-score of -3.0 or below, who have not yet had an osteoporotic fracture.

Strontium ranelate is also available on the PBS (for use as a sole antiresorptive agent) for osteoporosis in women aged ≥ 70 years with a bone mineral density (BMD) T-score ≤ –3.0.

Secondary prevention

Bisphosphonates

Alendronate and risedronate reduce the relative risk of vertebral fractures by about 50% in postmenopausal women with osteoporosis,^25-27 and appear to have a similar effect in men.²⁸ There is a lesser reduction in hip fractures,²⁹ and limited evidence of a reduction in wrist fractures with alendronate.²⁵ Calcium can impair bisphosphonate absorption, and the two should not be taken at the same time of day. Bisphosphonates can cause upper GI symptoms, which limits their tolerability, and should be taken at least 30 minutes before meals with a full glass of water to allow adequate absorption. Patients should remain upright for at least 30 minutes after taking each dose. They should not generally be used in patients whose glomerular filtration rate (GFR) is below 35 ml/minute.

Raloxifene

Raloxifene inhibits bone resorption, but does so without breast or uterine stimulation. Breast cancer incidence has been shown to be reduced in raloxifene users.³⁰ Raloxifene has been shown to reduce the incidence of vertebral fractures by 36%, but has not been shown to reduce the incidence of non-vertebral fractures.³¹ It increases the risk of deep venous thrombosis, similar in degree to that seen in hormone replacement therapy users,³⁰ but does not help relieve menopausal symptoms.

Strontium ranelate

Strontium ranelate is a new agent which inhibits bone resorption and may also stimulate formation.³² It is also listed on the PBS for treatment of osteoporosis in women. It has been shown to reduce vertebral fractures by 41% in a three year study period³² and non-vertebral fractures in total by 16%.³³ It appears to be well tolerated, although there is an increase in the risk of deep venous thrombosis. Patients should not take calcium supplements at the same time of day as the strontium. The incorporation of strontium into bone tissue can make ongoing monitoring of BMD by DEXA less accurate, although device software may provide some compensation for this effect.

Bisphosphonates and osteonecrosis of the jaw

Considerable attention has been given in the scientific literature and the general media to the issue of osteonecrosis of the jaw (ONJ) and bisphosphonate use. It appears to be rare (estimated as being between 1 in 10,000 and 1 in 100,000 patient treatment years per event) when these agents are taken orally in patients with uncomplicated osteoporosis. It is more common (estimated as being between 1 in 10 and 1 in 100 patient treatment years per event) in patients using intravenous agents for treatment of cancer.^34-36 Ensuring optimal oral and dental health before prescribing seems prudent, as the risk increases after dental extraction. The optimal interval between cessation of bisphosphonate therapy and safe dental extraction is not known.

Table 2: Specific osteoporosis therapies

Drug class	Formulations available/brand	Dosing regimens	Indicated for primary fracture prevention?	Indicated for secondary fracture prevention
Calcium	Multiple – calcium carbonate Citracal – calcium citrate	1200 mg daily (2 tabs) 500 mg daily (2 tabs)	Yes	Yes
Vitamin D	Multiple – vitamin D3 (cholecalciferol) preferred	600 – 1000 IU daily Note: 2 tabs daily of ‘Ostelin Vitamin D plus Calcium’ will satisfy both requirements	Yes	Yes
Bisphosphonates
Alendronate	Alendronate 10 mg Alendronate 70 mg (generic available; Fosamax; Fosamax Plus - contains 2800 IU vitamin D3)	Once daily Once weekly	Yes	Yes
Risedronate	Actonel 5 mg Actonel 35 mg Actonel Combi (includes calcium carbonate tablets equivalent to 500mg calcium)	Once daily Once weekly Risedronate once weekly, calcium the other 6 days	Yes	Yes
	Actonel Combi D (includes calcium carbonate plus cholecalciferol sachets equivalent to 1g calcium, 880 IU vitamin D3)	Risedronate once weekly, sachets the other 6 days	Yes	Yes
Etidronate*	Didrocal (etidronate 200 mg, packaged with calcium carbonate 500 mg)	3-monthly cycle - etidronate daily for 14 days, calcium for 76 days	No	Yes
Raloxifene	Evista 60 mg	Once daily	No	Yes
Strontium ranelate	Protos 2 g sachets	Once daily	Women only	Yes
Teriparatide**	Forteo 20 μg injection	Daily injection	No	Yes

^*No longer recommended as first line bisphosphonate

^**Should only be recommended after consultation with endocrinologist

Tell your veteran patients that…

• osteoporosis is preventable and treatable.
• osteoporosis can result in fractures which in turn can have serious health consequences.
• specific osteoporosis treatments (such as bisphosphonates) are effective but need to be taken for several years to have their full effect.

Suggested further reading

• The Burden of Brittle Bones: Epidemiology, Costs & Burden of Osteoporosis in Australia: Department of Medicine, University of Melbourne; 2007. This is available at https://www.iofbonehealth.org/sites/default/files/PDFs/white_paper_australia-23-06-08.pdf
• Häuselmann HJ, Rizzoli R. A comprehensive review of treatments for postmenopausal osteoporosis. Osteoporosis International 2003;14(1):2-12.
• Ebeling P. Osteoporosis in men. New Eng J Med 2008;358(14):1474-1482
• Diamond T, Eisman JA, Mason RS, Nowson C, Pasco JA, Sambrook P, et al. Vitamin D and adult bone health in Australia and New Zealand: a position statement. MJA 2005;182(6):281-5.
• The Australian fracture risk calculator estimates absolute fracture risk, taking into account individual patient factors. It is available at http://www.garvan.org.au/bone-fracture-risk

References

1. The Burden of Brittle Bones: Epidemiology, Costs & Burden of Osteoporosis in Australia: Department of Medicine, University of Melbourne, 2007. Available from: http://www.osteoporosis.org.au/files/research/burdenbrittle_oa_2007.pdf
2. Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA, Berger M. Patients with Prior Fractures Have an Increased Risk of Future Fractures: A Summary of the Literature and Statistical Synthesis. Journal of Bone and Mineral Research 2000;15(4):721-39.
3. Center JR, Bliuc D, Nguyen TV, Eisman JA. Risk of Subsequent Fracture After Low-Trauma Fracture in Men and Women. JAMA 2007;297(4):387-94.
4. Eisman J, Clapham S, Kehoe L. Osteoporosis Prevalence and Levels of Treatment in Primary Care: The Australian BoneCare Study. Journal of Bone and Mineral Research 2004;19(12):1969-75.
5. Assessment of fracture risk and its implication for screening for postmenopausal osteoporosis. Geneva: WHO, 1994.
6. Ebeling P. Osteoporosis in Men. New Eng J Med 2008;358(14):1474-82.
7. Berris K, Repp A, Kleerekope M. Glucocorticoid-induced osteoporosis. Curr Opin Endocrinol Diabetes Obes 2007;14(6):446-50.
8. Mattson RH, Gidal BE. Fractures, epilepsy, and antiepileptic drugs. Epileps Behav 2004;5(Supplement 2):36-40.
9. Hugenholtz GWK, Heerdink ER, van Staa TP, Nolen WA, Egberts ACG. Risk of hip/femur fractures in patients using antipsychotics. Bone 2005;37(6):864-70.
10. NPS News. 2007 [cited; 53:] Available from: http://www.nps.org.au/site.php?content=/html/news.php&news=/resources/NPS_News/news53
11. O'Neill S, MacLennan A, Bass S, Diamond T, Ebeling P, Findlay D, et al. Guidelines for the management of postmenopausal osteoporosis for GPs. Aust Fam Physician 2004;33(11):910-9.
12. Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ 1996;312(7041):1254-9.
13. Poole KES, Compston JE. Osteoporosis and its management. BMJ 2006;333(7581):1251-6.
14. Lafleur J, McAdam-Marx C, Kirkiness C, Brixner D. Clinical Risk Factors for Fracture in Postmenopausal Osteoporotic Women: A Review of the Recent Literature. Ann of Pharmacotherapy 2008(Jan 29 Epub ahead of print).
15. Ebeling P, Eisman JA. Recommendations from the Calcium and Vitamin D Forum. Medicine Today 2005;6(5):43-50.
16. Diamond T, Eisman JA, Mason RS, Nowson C, Pasco JA, Sambrook P, et al. Vitamin D and adult bone health in Australia and New Zealand: a position statement. Med J Aust 2005;182(6):281-5.
17. Prescribing Practice Review 39 Preventing osteoporosis and reducing fracture risk. National Prescribing Service; Sept 2007. Available from: http://www.nps.org.au/site.php?content=/html/ppr.php&ppr=/resources/Prescribing_Practice_Reviews/ppr39#PPRRefs
18. Morris H, Morrison G, Burr M, Thomas D, Nordin B. Vitamin D and femoral neck fractures in elderly South Australian women. Med J Aust 1984;140:519-21.

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