The bones of musculoskeletal health

Damien O’Brien MPSI provides a synopsis of bone health, including some of the more common conditions, investigations and treatments

Introduction

Bone health is an important aspect of overall health, and plays a particularly important role as an individual ages. Bones have many important functions in the body, including protecting organs, providing structure for soft tissue, facilitating breathing, and storing calcium. Bone is a specialised connective tissue with an internal matrix, which helps to give bone rigidity.

Osteoblasts are bone cells that are involved in formation of bone, while osteoclasts are involved in resorption of bone. Bone remodelling is the process of bone turnover by resorption and formation of bone tissue. Bone remodelling continues throughout life and is driven by physiological needs.¹ Bone health is a life-long concern, where bone mass peaks in adulthood and then decreases with age. Several conditions are associated with bone health and include osteopenia, osteoporosis, osteomalacia, rickets, and Paget’s disease of bones.²

There are several lifestyle modifications that can be recommended to improve bone health. Smoking and alcohol intake are associated with reduced bone health, and therefore smoking cessation and reducing alcohol intake are important steps. Weight-bearing physical activities also help to improve bone health. Calcium and vitamin D are required to maintain bone health, which can be achieved through diet or supplementation. There are many dietary sources of calcium, including dairy products, green leafy vegetables, and liver. Sources of vitamin D include fish, eggs, liver and sunlight. Calcium and vitamin D supplementation is recommended for individuals with a low dietary intake to raise these levels to normal levels.³

Diagnosis

Dual-energy x-ray absorptiometry (DXA) scans have been established by the World Health Organisation (WHO) as the best method for assessing bone mineral density (BMD). After a DXA scan, a t-score is obtained, which shows the difference between the bone mineral density in the subject and the mean value of bone mineral density in a young adult. This is measured in standard deviations from the mean and is required to diagnose common bone conditions.

Fracture Risk Assessment Tool (FRAX) is a validated risk assessment tool by the WHO that provides a 10-year probability of a major fracture. It considers body mass index and other independent risk factors and is useful in determining which individuals may need intervention.⁴

Osteopenia and osteoporosis

Osteopenia is characterised by a decrease in BMD below normal values, but not low enough to meet the criteria for osteoporosis. Osteopenia is defined as a t-score between -1 to -2.5, while osteoporosis is a t-score below -2.5. Both conditions are as a result of an imbalance between bone formation and resorption, causing a net loss of bone mass and an increased risk of fractures. They can often progress without symptoms until a fracture occurs, with fractures leading to a large decrease in quality of life, increasing morbidity, disability and mortality.

There are several risk factors that increase the likelihood of developing osteopenia and osteoporosis. Increasing age is a major risk factor, with a gradual decrease in bone density observed as an individual ages. Being female is another risk factor, particularly postmenopausal women due to lower levels of oestrogen. Other risk factors include smoking, low body weight, early menopause, sedentary lifestyle, family history of osteoporosis, excessive alcohol intake, and medications including corticosteroids and anticonvulsants.

Pharmacological treatment may be initiated in patients in osteopenia but is based on the FRAX score, while pharmacological treatment is generally indicated for patients with osteoporosis. Lifestyle modifications including improving nutrition, weight-bearing activities and smoking cessation, and reducing alcohol intake should be encouraged in all patients.^4,5

The primary objectives of osteoporosis treatment are to preserve bone density, prevent fractures and improve overall bone health. Pharmacological treatment is very important in the management of osteoporosis. Bisphosphonates are the most commonly used class of drug to treat osteoporosis. They work by inhibiting osteoclast activity, which decreases bone resorption and therefore reduces loss of bone density.

Bisphosphonates are indicated for treatment of osteoporosis in postmenopausal women and men at high risk of fractures. Oral bisphosphonates can cause stomach upset and oesophagus erosion, which can be reduced by remaining seated upright or standing for 30-to-60 minutes after administration. Patients who have been on bisphosphonates for more than five years should be assessed due to an increased risk of femoral fractures and osteonecrosis of the jaw.

Examples of bisphosphonates include alendronate, ibandronate, risedronate and zoledronic acid. Alendronate is generally a 70mg tablet administered once weekly, risedronate is a 35mg tablet administered once weekly, and ibandronate is a 150mg tablet administered once per month. Zoledronic acid is administered as an intravenous infusion once per year.^4,6,7

Denosumab is a monoclonal antibody that targets the receptor activator of nuclear factor kappa-B (RANK) ligand. This inhibits osteoclast activity, preventing loss of bone density and reducing the risk of fractures. It is administered as a 60mg subcutaneous injection every six months. Denosumab is indicated for the treatment of osteoporosis in postmenopausal women who have an increased fracture risk. Denosumab may not be as effective in the treatment of men, but it is effective in treating bone loss associated with hormone ablation therapy or long-term corticosteroid treatment.

The safety and efficacy of denosumab is maintained over 10 years of treatment, with a long-term management plan recommended to ensure treatment is not stopped or delayed. Hypocalcaemia is an adverse effect that is more likely in patients with renal impairment, which should be monitored. Other adverse effects include infection, osteonecrosis and bone, joint or muscle pain.^4,6,7

Teriparatide is a synthetic form of parathyroid hormone and stimulates osteoblast activity and therefore bone formation. Teriparatide is indicated for patients with severe osteoporosis or those who can’t tolerate other treatment options. It is administered as a 20mcg subcutaneous injection daily for 24 months. The patient should have a repeat DXA scan, and a new treatment plan implemented. Parathyroid hormone levels, serum and urinary calcium, vitamin D levels and renal function should be investigated before commencing teriparatide treatment. Adverse effects of teriparatide include hypercholesterolemia, low mood, nausea, vomiting and muscle cramps.^4,6,7

Selective oestrogen receptor modulators (SERMs) work by imitating the effect of oestrogen on bone tissue, which promotes bone formation and reduces bone resorption. They are approved for the prevention and treatment of osteoporosis in postmenopausal women, but not in men. Raloxifene is administered orally as a 60mg dose daily. It is associated with a small increase in the risk of venous thromboembolism and should be used with caution in patients with a history of stroke or with risk factors for stroke.^4,6,7

Osteomalacia and rickets

Vitamin D, calcium and phosphorus are three of the main factors that have an influence on bone maturation and mineralisation. Reduced mineralisation can lead to rickets and/or osteomalacia. 

Rickets is characterised by a defect in mineralisation and the widening of the epiphyseal plates, while osteomalacia is characterised by a defect in the mineralisation of the bone matrix. Rickets and osteomalacia generally both occur in children. Rickets occurs only in children, while adults can develop osteomalacia after epiphyseal plate fusion. Vitamin D deficiency is the most common cause of both osteomalacia and rickets, which can be due to decreased vitamin D production, decreased vitamin D absorption, or altered vitamin D metabolism. Decreased vitamin D production can be due to reduced sunlight exposure, obesity or ageing. Decreased vitamin D absorption can be due to malabsorptive conditions such as Crohn’s disease, cystic fibrosis, coeliac disease and cholestasis. Chronic kidney disease and liver disease can lead to altered vitamin D metabolism.

Certain medications, including phenobarbital, phenytoin, carbamazepine, isoniazid, rifampicin, theophylline, ketoconazole and corticosteroids, can cause vitamin D deficiency. In rarer cases, nutritional deficiency of calcium or phosphorus can result in these conditions.^8,9

Softening of the skull bone, deformities of the weight-bearing limbs, including bowlegs and knock knees and spinal column deformity are some of the most common symptoms of rickets. Gait disturbance, growth retardation and bone pain can also be symptoms. Treatment includes both an early intensive phase and a late maintenance phase. There are several treatment regimens to treat nutritional deficiency of vitamin D, comprising either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) administration, with monitoring for healing. The intensive phase of treatment is generally for two-to-three months, with calcium supplementation often necessary.^8,9

Symptoms of osteomalacia are generally non-specific and can include proximal muscle weakness, muscle spasms, altered gait, spinal deformities, bone pain and increased falls.^8,9 It is necessary to establish the aetiology of osteomalacia in order to decide on the treatment. Treatment should be based on reversing the underlying condition and correcting the vitamin D or other nutritional deficiency. In patients with severe vitamin D deficiency, the following may be a dosing strategy:

• 50,000 IU of vitamin D2 or vitamin D3 once per week for eight-to-12 weeks, followed by:
• 800 IU–2000 IU of vitamin D3 daily.^8,9

Paget’s disease of bone

Paget’s disease is a skeletal growth disorder with unusual bone growth abnormalities occurring in multifactorial ways and is often characterised by diffuse pain in the musculoskeletal system. There is a strong genetic predisposition to Paget’s disease of bone. It presents with excess osteoclast activity followed by an increase in osteoblast activity, leading to the formation of weaker bones that are more susceptible to fracture.

The condition can affect one or more bones, with the axial skeleton most often involved (spine, pelvis and skull). A complication of Paget’s disease is the development of sarcomatous tumours. Patients who don’t have abnormal blood tests and are asymptomatic may not require treatment. Patients who have abnormal bone defects, skull deformities, involvement of weight-bearing bones or severe diffuse pain may receive pharmacological treatment.

Treatment options aim to prevent bone breakdown and the subsequent bone formation. Bisphosphonates are often used as first-line treatment because of their influence on bone remodelling. Denosumab is used in cases of bisphosphonate intolerance or contraindication and has shown efficacy. Calcium and vitamin D supplementation may provide some symptomatic relief. Pain may be managed with paracetamol or non-steroidal anti-inflammatories (NSAIDs). Surgery may be used for patients who have progressed to developing an osteosarcoma.¹⁰

Role of the pharmacist

Pharmacists play an important role in bone health through medication management, patient education and collaboration with other healthcare professionals. Pharmacists can be involved in medication management programmes to ensure optimised treatment plans are in place for patients.

Pharmacists also have an important role in patient education on lifestyle modifications that are important in improving bone health. They can counsel patients on adverse effects of treatment and the importance of adherence to medication. Additionally, pharmacists can monitor for potential drug interactions when initiating pharmacological therapy to improve bone health. Finally, pharmacists can work closely with other healthcare professionals to ensure comprehensive care for patients with bone health issues to improve bone health and quality of life.^11.12