Osteoporosis in people with severe mental illness: A forgotten condition
Article Outline
Keywords: Severe mental illness, Antipsychotic, Hyperprolactinaemia, Osteoporosis
Schizophrenia and bipolar disorder are severe mental illnesses (SMI) that affect around 1% of the population. They are amongst the leading causes of disability and impact social, work, occupational, interpersonal and self-care functioning. Following the introduction of antipsychotic medication in the 1950s, the lives of many people with SMI have been transformed with steadily fewer psychiatric in-patients and increased independence in the community.
As treatments of psychosis have improved, there has been an increasing awareness of the need for high quality physical health care for those with SMI. Schizophrenia is associated with a threefold increased risk of premature death, and shortened life expectancy of 10–20 years. Although suicide and trauma are important causes of death, around three quarters of all deaths are attributable to physical illness, with cardiovascular disease being the commonest cause of death.
Obesity and metabolic problems are being increasingly recognised and managed but an appreciation of bone health has lagged behind. Studies defining the increased risk of osteoporotic fracture and earlier onset of osteoporosis in people with SMI are only just starting to appear [1]. A UK General Practice Research Database study showed that the relative risk of fracture at any site was increased 2.5-fold in premenopausal women with psychotic disorders while hip fracture rates were increased 5.1- and 6.4-fold in older women and men respectively [2]. A Danish study also found a 1.2-fold increased fracture risk in those taking antipsychotics [3] while a Dutch population based case-control study reported a 1.68- and 1.33-fold increased risk for hip or femur fracture for current and past users of antipsychotics respectively [4].
The impact of fracture, at least at the hip, is greater in people with SMI with higher post-operative infection rates, worse 1-year ambulatory outcomes and higher rate of contralateral fracture [1]. A fracture may also precipitate deterioration of the mental state contributing to lack of motivation and adherence to rehabilitation.
Reduced bone mineral density (BMD) occurs in people with SMI for many reasons including an increased prevalence of traditional risk factors, such as reduced calcium and vitamin D intake, reduced physical activity, increased alcohol intake and smoking, as well as disease specific factors, such as hypercortisolaemia and psychogenic polydipsia with obligatory hypercalcuria.
There are also concerns that treatment with certain antipsychotics may also lead to the development of osteoporosis; indeed the epidemiological studies suggest a closer association between the risk of osteoporotic fracture and treatment than with the illness [1].
The most likely mechanism linking antipsychotics with decreased BMD is through hyperprolactinaemia and secondary suppression of sex steroids. Studies of people with prolactinoma have demonstrated that chronic hyperprolactinaemia is associated with reduced bone mineral density (BMD) and a 2–4.5-fold increased risk of osteoporotic fracture [1]. Similarly in patients with SMI, prolactin concentrations have been shown to be inversely associated with BMD.
The prevalence of hyperprolactinaemia is higher in people receiving antipsychotics than virtually any other patient or population group. Cross-sectional studies have indicated that the prevalence of hyperprolactinaemia ranges from 42% to 93% in women and 18–72% in men [5]. Adolescents and women of reproductive age, particularly parous women, appear to be at particularly high risk of hyperprolactinaemia.
Hyperprolactinaemia varies markedly between antipsychotics [5]. First generation antipsychotics are associated with hyperprolactinaemia in 33–87% of cases depending on the dose, while amongst the second generation antipsychotics, amisulpride has the greatest potential to increase prolactin, with nearly all patients developing hyperprolactinaemia even at low doses. Risperidone and paliperidone are also associated with high rates of hyperprolactinaemia but other second generation antipsychotics are associated with much lower rates. Aripiprazole is associated with the lowest rates (3.1–5%) while clozapine is associated with hyperprolactinaemia in fewer than 5% of cases. Hyperprolactinaemia is reported in 0–29% and 6–40% of people receiving quetiapine and olanzapine respectively.
These differences appear to translate into differences in bone health as cross-sectional studies comparing prescriptions of olanzapine with first generation antipsychotics found individuals taking olanzapine had higher BMD [1]. Furthermore the Dutch case-control study showed the fracture rate was only increased in those prescribed first generation antipsychotics [4].
The increase in osteoporotic fracture has clinical implications for the management of SMI. First caution is needed when antipsychotics that lead to sustained hyperprolactinaemia are used in adolescents. Puberty is a critical period of bone formation and 90% of peak bone mass is accrued by the age of 19 years. Childhood bone mass is a determinant of adult bone mass and this tracks well past the menopause. Mathematical models demonstrate that differences in peak BMD affect the onset of osteoporosis to a greater extent than menopausal age or rate of bone loss in adulthood suggesting that drugs that compromise peak BMD may have long lasting effects on fracture risk [1].
People with SMI should be assessed for risk factors for osteoporosis and offered dual energy X-ray absorptiometry where appropriate to identify those with low BMD. The treatment of osteoporosis is similar to the general population. Weight bearing exercise should be encouraged and it is advisable to supplement those at risk of dietary deficiency with 1
g of calcium and at least 400–800IU/day of vitamin D. Anti-catabolic agents (e.g. bisphosphonates) or anabolic agents (e.g. parathyroid hormone) can be used as in the general population.
It has been estimated that only 10–20% of UK women with osteoporosis receive drug treatment for the condition. Although data are not available, it seems likely that even fewer people with SMI are receiving treatment for osteoporosis as these individuals are generally less likely to take up preventative medical care and screening.
It is therefore the responsibility of those caring for people with SMI to consider osteoporosis and take steps to prevent and treat this to reduce the risk of fracture. Further prospective research, however, is needed to provide clear evidence for the development of screening guidelines for people with SMI as well as identifying the most cost-effective treatments to prevent fractures in those at highest risk.
Provenance and peer review
Commissioned, not externally peer reviewed.
Disclosure
Professor Holt has undertaken lectures for Astra Zeneca, Eli Lilly, GlaxoSmithKline, and Novo Nordisk. He has served on advisory boards for Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharpe and Dohme and Novo Nordisk. He has received funding to attend conferences Astra Zeneca, Eli Lilly, GlaxoSmithKline, Novo Nordisk.
Funding
Funding for Osteoporosis Editorial: Professor Holt is an employee of the University of Southampton. No additional funding was used in the writing of this article.
References
- . Understanding osteoporosis. J Psychopharmacol. 2008;22(2 Suppl.):38–45Mar
- . Sex- and age-specific incidence of fractures in mental illness: a historical, population-based cohort study. J Clin Psychiatry. 2008;69(9):1398–1403Sep
- . Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int. 2006;17(6):807–816
- . Antipsychotic use and the risk of hip/femur fracture: a population-based case–control study. Osteoporos Int. 2009;20(9):1499–1506Sep
- . A review of the association between antipsychotic use and hyperprolactinaemia. J Psychopharmacol. 2008;22(2 Suppl.):46–55Mar
PII: S0378-5122(10)00230-6
doi:10.1016/j.maturitas.2010.06.004
© 2010 Elsevier Ireland Ltd. All rights reserved.
