Managing osteoporosis in the pharmacy

The need to preserve bone density, prevent fractures, and improve overall bone health is the mainstay of osteoporosis treatment and management

Introduction

Osteoporosis is a skeletal disorder characterised by low bone mineral density (BMD) and caused by altered bone microstructure. Osteoporosis increases the risk of fractures, which can significantly decrease quality of life, leading to increased morbidity and mortality. Often referred to as a silent condition, it can progress without symptoms until a fracture occurs. It primarily affects older individuals, particularly postmenopausal women, but can also affect men and younger individuals.

Osteoporosis is a major public health concern, especially due to the aging population. It is estimated that approximately 300,000 people in Ireland currently have osteoporosis. Pharmacists play a crucial role in osteoporosis management, particularly in prevention, patient education, pharmacological treatment, and non-pharmacological treatment.^1,2

Background

Osteoporosis is a multifactorial condition caused by an imbalance of bone resorption and bone formation, leading to a net loss of bone mass. The remodelling of bone tissue is a continuous process in normal bone. Osteoclasts are bone cells that degrade the bone matrix, while osteoblasts are responsible for forming bone tissue. A decrease in BMD occurs when osteoclastic activity exceeds osteoblastic activity. Several risk factors increase the likelihood of developing osteoporosis, including age, female gender, early menopause, smoking, sedentary lifestyle, low bodyweight, family history, excessive alcohol intake, and certain medications.¹

Primary osteoporosis is the most common form of osteoporosis and generally affects older individuals. Primary osteoporosis can be due to the natural drop in oestrogen levels post-menopause, as oestrogen plays an important role in maintaining bone density. It can also result from reductions in bone formation, occurring in both men and women, typically after the age of 70 years. In most individuals, peak bone mass is achieved in their third decade and bone resorption exceeds bone formation thereafter.

Secondary osteoporosis occurs due to other medical conditions or the treatment of medical conditions. Medical conditions that may contribute to osteoporosis include hyperthyroidism, hyperparathyroidism, malabsorption, and rheumatoid arthritis. Medications that may cause secondary osteoporosis include corticosteroids, anticonvulsants, and proton pump inhibitors.¹

Osteoporosis often has no symptoms until an osteoporotic fracture occurs. Osteoporotic fractures occur in situations where you would not expect a person to fracture a bone. The most common osteoporotic fractures are of the spine, wrist, shoulder, and hip. Fractures of the spine can result in chronic pain, reduced mobility, stooped posture, and loss of height. Fractures of large bones can significantly reduce mobility and can be associated with risks, including deep vein thrombosis and pulmonary embolism. The lifetime risk of osteoporotic fracture is high, with approximately one in three females and one in five males over the age of 50 experiencing an osteoporotic fracture.^1,3

Osteoporosis is diagnosed by measuring bone mineral density using dual-energy X-ray absorptiometry (DXA). The World Health Organisation has established these diagnostic criteria. A BMD score that is 2.5 standard deviations or more below the average for a young adult of the same gender is considered diagnostic of osteoporosis. A BMD measurement between 1 and 2.5 standard deviations below the average value is classified as osteopenia. Additional investigations may be required if bone loss due to conditions other than aging or menopause is suspected, with tests for hyperthyroidism and hyperparathyroidism being useful. The Fracture Risk Assessment Tool (FRAX) is a validated risk assessment tool used in osteoporosis management, providing a 10-year probability of a major fracture. This tool is useful in identifying patients with osteopenia who require pharmacological intervention.^1,3

Non-pharmacological treatment

The primary objectives of osteoporosis management are to preserve bone density, prevent fractures, and improve overall bone health. Non-pharmacological interventions are vital in the prevention and treatment of osteoporosis. As tobacco smoking and excessive alcohol consumption contribute to bone loss, individuals should be encouraged to participate in smoking cessation programmes and moderate their alcohol intake.

Weight-bearing and resistance exercises help to improve balance and reduce the risk of fractures and falls. Strength training, walking, and jogging are examples of exercises that should be encouraged. Non-weight bearing exercises have other health benefits, but not necessarily for bone health. Individuals should maintain an ideal body weight as low body weight is correlated with low BMD and excessive body weight is associated with an increased risk of fractures. Fall prevention strategies, including removing tripping hazards and the use of walking aids, can be useful in reducing the risk of fractures.¹

Nutrition is an important element of osteoporosis prevention and management. Calcium is a primary constituent of bone tissue and is therefore an important mineral for bone health. Low dietary calcium intake can lead to decreased bone mineralisation and contribute to osteoporosis. Dairy products, leafy green vegetables, and fish are all dietary sources of calcium. Vitamin D is important for calcium absorption and utilisation in the body. Vitamin D can be obtained from sunlight and through the diet from meat, fish, and liver. Calcium and vitamin D supplements are recommended if dietary intake is insufficient.

Adequate dietary protein intake is important in supporting bone formation and maintaining muscle mass, which is essential for preventing falls. Dairy products, meat, and fish are examples of dietary protein sources. Finally, magnesium is important in bone mineralisation and regulating calcium metabolism, and is found in leafy vegetables, nuts, and seeds. Adequate intake of these nutrients can support bone health, reducing the risk of osteoporosis.^1,4 

Pharmacological treatment

Pharmacological treatment is the cornerstone of the management of osteoporosis. Osteoporotic fractures can be reduced by pharmacological treatment. Pharmacological treatment of osteoporosis can be anti-resorptive (inhibiting osteoclastic activity) or bone-forming (stimulating osteoblastic activity). The anti-resorptive treatment options are bisphosphonates, receptor activator of nuclear factor kappa-B (RANK) ligand inhibitors, and selective oestrogen receptor modulators (SERMs). Teriparatide is a synthetic form of parathyroid hormone that promotes bone formation.⁵

Bisphosphonates are a class of drugs that work by inhibiting osteoclast activity, which decreases bone resorption and therefore reduces loss of bone density. They are indicated for the treatment of osteoporosis in postmenopausal women and men at high risk of fractures. They are the most commonly used class of drugs to treat osteoporosis. Alendronate, risedronate, and ibandronate are all administered orally. Alendronate and risedronate are generally administered once weekly, while ibandronate is administered once per month. Zoledronic acid is administered as an intravenous infusion once per year. All oral bisphosphonates are associated with upper gastrointestinal adverse effects, including gastrointestinal reflux, oesophagitis, gastritis, and oesophageal or gastric ulcers. Patients should take oral bisphosphonates as the first medication in the morning and more than 30 minutes before the first food intake, while remaining seated upright or standing for 30-60 minutes to reduce gastrointestinal adverse effects.

Other adverse effects of bisphosphonates include femoral fractures and osteonecrosis of the jaw. Administration of bisphosphonates leads to accumulation of bisphosphonates in bone, which is the reason bisphosphonates may be discontinued in some cases after five years. An individual assessment of benefits and risks of serious adverse effects should be performed before discontinuing therapy.^5,6

Denosumab is a monoclonal antibody that inhibits receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab prevents the activation of osteoclasts, thereby reducing bone resorption and preventing the loss of bone mass. It is indicated for the treatment of osteoporosis in postmenopausal women and men who are at a high risk of fracture. It is also effective in the treatment of bone loss associated with hormone ablation therapy or long-term corticosteroid therapy. It is administered as a 60mg subcutaneous injection every six months. Denosumab is generally well-tolerated, with the safety and efficacy of denosumab maintained over 10 years of treatment. A long-term individualised osteoporosis treatment plan is recommended to ensure treatment is not stopped or delayed, as discontinuation can result in a rebound activation of bone resorption. Denosumab is generally well-tolerated, with nausea, vomiting, weakness, and infection among the most common adverse effects. Osteonecrosis of the jaw and atypical femoral fracture are more serious but rarer adverse effects. Hypocalcaemia is more likely in patients with renal impairment and may require monitoring.^5,7

SERMs exert their mechanism of action by imitating the effect of oestrogen on bone tissue, promoting bone formation, and reducing bone resorption. In postmenopausal women, the drop in oestrogen levels favours bone resorption, leading to a decrease in bone mass. Raloxifene is an example of a SERM that inhibits bone resorption and increases BMD by mimicking oestrogen in bone tissue. It is indicated for prevention and treatment of postmenopausal osteoporosis. Raloxifene is administered orally as a 60mg dose daily. The most common adverse effects of raloxifene include hot flushes, flu-like symptoms, and muscle spasms. It is also associated with a small increase in the risk of venous thromboembolism and therefore should be used with caution in patients with a history of stroke or with risk factors for stroke.^5,8

Teriparatide is a synthetic form of parathyroid hormone and stimulates bone formation through osteoblastic activity. Bone undergoes resorption to a greater extent than formation when under continuous exposure to parathyroid hormone, as in hyperparathyroidism. However, exposure to low-dose parathyroid hormone causes greater bone formation than resorption. Therefore, teriparatide is administered as a 20mcg subcutaneous injection daily for 24 months, followed by a repeat DXA scan and review of the treatment plan. A significant reduction in vertebral fractures has been demonstrated with teriparatide. It is indicated for use in both men and women at high risk of fractures, and it is also useful in treating secondary osteoporosis associated with systemic corticosteroid use. Teriparatide is generally well-tolerated, with potential adverse effects including nausea, headache, dizziness, leg cramps, and mild hypercalcaemia.^5,9

Role of the pharmacist

Pharmacists play a vital role in the prevention and treatment of osteoporosis. Pharmacists are ideally placed to educate patients on the importance of nutrition, weight-bearing exercise, smoking cessation, and moderating alcohol intake in improving bone health. Pharmacists have the expertise to contribute to an osteoporosis medication management plan for patients. Pharmacists also have an important role in patient counselling on the proper use of medications, including dosing regimens, adverse effect management, and the importance of medication adherence. Finally, pharmacists can collaborate with other healthcare professionals to ensure optimal management of osteoporosis.