Glucocorticoids are steroid hormones that have been in use for over 65 years to treat inflammatory conditions such as rheumatoid arthritis. While their potency in eliminating inflammation is well known, until recently little attention has been paid to the various side effects and conditions that arise from continued use of these drugs. The most common adverse outcomes are seen in bone and muscle metabolism. These include osteoporosis, osteonecrosis, myopathy, and sarcopenia. Other common risks include diabetes, obesity, dyslipidaemia, skin atrophy, hypertension, changes in growth and sex hormones, glaucoma, cataracts, delayed wound healing, and increased risks of infection. Osteoporosis is another possible side effect, characterized by loss of bone tissue. Below we discuss the consequences and prevention strategies for Glucocorticoid-induced osteoporosis, a significant concern for patients undergoing long-term glucocorticoid treatment.
Glucocorticoid-induced osteoporosis remains largely underdiagnosed and undertreated in the healthcare system. Close to 80% of all bone fractures, primarily in the spine, proximal femur and ribs, are caused precisely by unmonitored glucocorticoid use. In fact, about 25% of all treated patients experience a fracture within the first 12 months, a number that increases up to 50% within 5 – 10 years. Despite the existing risks, therapeutic interventions by healthcare providers are not initiated as early as they ought to be. Part of the problem is due to inadequate research on drug mechanisms and lack of availability of clinical information.
What is known about the action of glucocorticoids in the body is that minimizing dosage and length of treatment are crucial in preventing adverse effects. Natural glucocorticoids are present in the human body at low concentrations and function in electrolyte and fluid control, homeostasis, fuel metabolism, and immune and stress responses. Specifically, glucocorticoids contribute to bone formation and maintenance, as well as calcium movement in the kidneys and intestines. Pharmacological doses of glucocorticoids interfere with these processes and result in decreased bone mineralization and loss of bone mass, which is greatest during the first 6-12 months of treatment, and can advance to as high as 15% per year. The highest risks are attributed to patients with the following:
- Treatment longer than 3 months
- High dose of glucocorticoid, or combination with other steroid drugs
- Over 60 years of age
- Low Body Mass Index (BMI)
- Low Bone Mineral Density (BMD)
Knowledge and timely application of glucocorticoid-induced osteoporosis prevention techniques can significantly minimize the risks. Before starting the glucocorticoid treatment, patients must undergo a bone health status evaluation by their doctors, which takes into account their estimated dietary calcium intake, sun exposure, physical activity levels, and risks factors. Additional pre-testing for renal and hepatic function, serum 25-hydroxyvitamin D, calcium, and sex hormone concentrations are also recommended. Patients should also be monitored throughout glucocorticoid therapy. Height loss of 3-5 cm may indicate vertebral fractures and should be addressed by the physician. Glucocorticoid-induced osteoporosis prevention intervention must be started at the same time as glucocorticoid therapy itself and continued without breaks throughout. Some studies indicate that Vitamin D and Calcium supplements may aid treatment.
As well, there exist prescription medications for glucocorticoid-induced osteoporosis. However, it is imperative to note that very little research has been conducted on the effects of these drugs on the body and they might carry substantial health risks. The 5 major classes of these drugs are outlined below.
- Bisphosphonates – These include Alendronate, Risedronate, Etidronate, and Zoledronic acid. Research on bisphosphontes shows an increase in BMD and decrease in fracture risk, but these studies were undertaken on women with postmenopausal osteoporosis, which is suspected to act via a different molecular mechanism than glucocorticoid-induced osteoporosis. Injection bisphosphonates may be pertinent to patients who have trouble adhering to a schedule of self-medication.
- Teriparatide – This osteoanabolic hormone may be beneficial for patients who are taking glucocorticoids in combination with other steroids. Once again, the increases in BMD and lower fracture risks have been assessed only in women with postmenopausal osteoporosis.
- Hormone Replacement Therapy – Intended to treat symptoms of hypogonadism, which in itself leads to bone loss and fractures, this treatment option still carries significant risks and should be applied only if bisphosphonates and teriparatide had been deemed ineffective.
- Raloxifene – Just like options 1 and 2, the increased BMD and decreased fracture risk was observed only in women with postmenopausal osteoporosis.
- Denosumab – This drug showed positive effects on hip and spine BMD in one study.
Ongoing research and development of novel glucocorticoids includes new oral medications, reduction of side effects in tissues other than bone, and reduction of hormonal effects that lead to glucose intolerance, diabetes, dyslipidaemia, and obesity, an area of vulnerability that has not previously been much researched.