Drug-induced Osteoporosis and the Local Pharmacy: An Ideal Setting for Effective Intervention to Identify and Inform High-risk Patients
Osteoporosis is a disease characterized by low bone mineral density and deterioration of the bone architecture leading to increased fragility and fractures. Primary osteoporosis indicates loss of bone mass due to aging and menopause. Secondary osteoporosis may be drug- or disease-induced; causes include exposure to glucocorticoid medications, use of antidepressants or anticonvulsants in pregnant women, proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs), thiazolidinediones (TZDs), anticonvulsants, calcineurin inhibitors, chemotherapy, anticoagulants, hypogonadism (low levels of testosterone), alcohol abuse, smoking, gastrointestinal disease, hypercalciuria, and immobilization. We briefly discuss here the association of these drug classes with osteoporosis.
Glucocorticoid induced osteoporosis:
Glucocorticoid-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis, the leading cause in the <50 years age group, and the chief iatrogenic cause of the disease. Prior and ongoing exposure to glucocorticoids (GCs) increases the risk of fracture and bone loss as the activity of inflammatory cells and bone cells are closely interrelated, and steroids not only suppress immune cells but also affect bone metabolism. The gold standard in the pharmacological treatment of glucocorticoid-induced osteoporosis in postmenopausal women is prophylaxis with bisphosphonates, which should be started soon after beginning chronic glucocorticoid therapy.
Hormonal deficiency, such as of testosterone, can result in osteoporosis in men, and may occur with use of drugs that inhibit or alter metabolism of sex hormones including aromatase inhibitors, gonadotropin releasing hormone(GnRH) and the use of depot medroxyprogesterone acetate (DMPA).
- Aromatase inhibitors (AI) can decrease the incidence of metastatic breast cancer but can also reduce BMD and increase fracture risk. Tamoxifen offers bone protection, the absolute risk increase for fragility fracture is 3.3% for anastrazole and 2.8% for letrozole.
- The gonadotropin releasing hormone agonist (GnRA), used in conjunction with tamoxifen or AI in chemotherapy may down regulate the secretion of FSH and LH, lead to suppression of ovarian function, estrogen production and also affect bone metabolism. Whether used alone or in combination with an AI or chemotherapy, goserelin or leuprolide (GnRAs) in premenopausal women causes a rapid decline in BMD of about 5 to 6% over 6 to 12 months.
- Depot medroxyprogesterone acetate (DMPA), which prevents pregnancy by inhibiting LH and FSH, also decreases peak bone mass and increase the risk of fragility fractures in 20-30 years old.
- Hyperthyroidism or over supplementation of thyroid replacement therapy, produce direct effects on bone remodeling that results in bone loss.
Anticonvulsants, by inducing CYP450 enzyme may increase the metabolism of vitamin D or reduce circulation estrogen levels, contributing to bone loss. In vitro studies have suggested that anticonvulsants directly inhibit osteoblasts, resulting in decreased bone formation. Prophylactic vitamin D supplementation at doses up to 2000 IU/day can be recommended for all patients initiating anticonvulsant therapy. Conventional treatment with bisphosphonates may be needed when the response to vitamin D is inadequate.
Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are two of the most widely prescribed classes of antidepressants. Serotonin plays an important role in bone physiology and its use produces detrimental effects on bone mineral density especially in pregnant mothers. The serotonin molecule is synthesized by two different genes at two different sites, and plays antagonistic functions on bone mass accrual at these two sites: when produced peripherally, serotonin acts as a hormone to inhibit bone formation. In contrast, when produced in the brain, serotonin acts as a neurotransmitter to exert a positive and dominant effect on bone mass accrual by enhancing bone formation and limiting bone resorption.
Past studies have shown that use of SSRIs can cause decreased bone mineral density and increase the risk of fractures in both adolescents and adults, thus high-dose folic acid tends to reverse the effects of the SSRI on bone. Clinicians should ensure appropriate calcium and vitamin D supplementation. Patients considering treatment with SSRIs who have other risk factors for osteoporosis or fracture might benefit from DXA or FRAX analysis.
Proton pump inhibitors:
Proton pump inhibitors (PPIs) irreversibly bind to the H+-K+-ATPase of the proton pump in parietal cells and possibly affect the vacuolar H+-ATPase in osteoclasts, leading to reduced bone density upon chronic use.
Prevention and Treatment
Awareness about osteoporosis, its risk factors, prevention, and treatment, are important public health outcomes. Knowledge of medications that can induce bone loss in all patient populations is important to prevent long-term complications from this disease, which may not appear until later in life. Thus, it is key to maximize bone mass during adolescence and throughout life.
The first step in prevention is adequate intake of calcium and vitamin D through diet, exogenous supplementation, or both. Women with low bone density should be offered effective pharmacotherapy to reduce their risks of fracture and associated complications.
Implications for Pharmacy Practice
Prevention of fractures is the ultimate goal of therapy and requires effective communication with patients and other health care professionals. Recognizing potential drug causes, monitoring therapy, and utilizing preventive measures can dramatically improve the quality of life for patients.
Community pharmacies are accessible and provide an ideal setting for osteoporosis risk assessment and patient screening. Pharmacists can play a pivotal role in identifying and providing care to patients with osteoporosis. Pharmacists’ intervention can play an important role in recognizing the potential for drug related osteoporosis and preventing associated fractures and injuries. Smoking, excessive alcohol use, and caffeine use should be discouraged.
Pharmacists can also offer smoking cessation counseling with OTC aids, such as transdermal nicotine. Another helpful point to remember is that thiazide diuretics have calcium-retaining properties and can be somewhat protective against the disease. Thus, thiazides should be recommended as first-line drugs for treating hypertension, especially for patients with risk factors for osteoporosis.
Pharmacists can educate patients and providers to help reduce the number and severity of osteoporotic fractures. Pharmacists are in a unique position to help reduce the burden of osteoporosis by improving the identification of high-risk patients for treatment, especially those on corticosteroid therapy. Results from several studies suggest that pharmacist identification and counseling of patients at risk for osteoporosis results in higher DEXA testing and improvements in calcium intake.
In addition pharmacists need to be familiar with drugs suspected of causing drug related osteoporosis and the risk of fracture associated with specific agents, in order to ensure that patients taking such drugs should receive a baseline risk assessment or be referred for BMD testing by DEXA scan. Pharmacists working in oncology clinics should include assessment of bone health as part of their direct patient care activities and be involved in treatment decisions for the prevention and treatment of osteoporosis.
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