Ciara Gavin MPSI takes a clinical look at the risk factors, management and treatment options for osteoporosis

Background

Osteoporosis, meaning ‘porous bone’, is a progressive disease that occurs when the body loses bone mass and increases bone fragility and susceptibility to fractures.1,2,3 Osteoporosis affects up to 50 per cent of women and 25 per cent of males over the age of 50.1 

In the general population, bone mass increases through childhood, peaks in adolescence, remains relatively constant in early/late adulthood, and declines in old age.4,5 The adult skeleton is continually remodelling through bone resorption followed by bone formation. Osteoclasts are involved in bone resorption and osteoblasts are involved in bone formation. The rate of remodelling is affected by many factors, including sex hormones, vitamin D and parathyroid hormone.4,5 When balance is altered for various reasons, this can then result in greater bone removal than replacement, which leads to the development of osteoporosis.5 

Osteoporosis is often considered a ‘silent disease’, with many patients not aware they have the condition until they have a fracture

Osteoporosis is often considered a ‘silent disease’, with many patients not aware they have the condition until they have a fracture. Due to the weakened bone condition, fractures can occur from mechanical forces that would not normally lead to a fracture, ie, a simple trip.2 Approximately 53 per cent of patients who suffer a hip fracture can no longer live independently and 28.7 per cent will die within 12 months of the fracture.2 In Ireland, €402 million per year is spent on treating falls and fractures in the elderly.4 Therefore, it is important to identify patients at risk, and diagnose osteoporosis early to try to counteract the progression of the condition.

Osteopaenia is considered the early-stage bone disease and places a person at a higher risk of developing osteoporosis.4

Risk Factors

Some risk factors for osteoporosis include:2,3,4 

▸ Postmenopausal women, as women lose up to 30 per cent of their overall bone mass when they go through menopause.3,4 

▸ Men aged over 50.

▸ Low BMI.

▸ Cigarette smoking.

▸ Excess alcohol — alcohol intake and fracture risk is dose-dependent.2

▸ Lack of physical activity — especially at a young age, when most bone is being formed.4

▸ Vitamin D deficiency.

▸ Low calcium intake.

▸ Family history of fractures is considered a strong risk factor, as approximately 80 per cent of bone is genetic.4

▸ Rheumatoid arthritis and diabetes — some medical conditions which are linked with low BMD or steroid use have increased risk factors for osteoporosis, however rheumatoid arthritis and diabetes has been found to increase risk of fractures independently of BMD or the use of steroids.2

▸ Women whose period starts later than the age of 15 or had early menopause are at higher risk for bone loss due to irregularities in sex hormones.4

The following are some examples of medications which are also associated with osteoporosis:

▸ Patients taking long-term oral corticosteroids.3

▸ Depo-Provera contraception is known to cause bone loss, especially when started earlier in life.4

▸ Chemotherapy.4

▸ Some antiepileptic medications (ie, phenytoin) interfere with calcium absorption and the production of vitamin D.4

▸ Proton pump inhibitors.4

The fracture risk assessment (FRAX) tool has been recommended by the WHO to evaluate the fracture risk of patients.2,4 This tool computes the 10-year probability of hip fractures or major osteoporotic fracture.2 NICE recommends the use of a risk assessment tool in all women aged over 65 and males over 75 years to aid identification of unknown osteoporosis.2

Diagnosis

Osteoporosis can be diagnosed by the presence of fragility fractures, measurement of bone mineral density or less commonly, bone biopsy.4

Early diagnosis is key to optimum results.4 DXA (dual-energy x-ray absorptiometry) scans are gold-standard for diagnosing osteoporosis.4 A DXA scan applied to the femoral neck is the preferred site by the World Health Organisation (WHO) and international osteoporosis foundation due to the higher predictive value for fracture risk.2,6 The spine is not recommended as a suitable site for diagnosis of osteoporosis in older patients, as there is a proportionally higher prevalence in degenerative changes, which would inflate the bone mineral density (BMD) score, however it is used as a site for assessing response to treatment.7

 BMD2 is used by the WHO for defining osteoporosis6 as BMD correlates with bone strength and can be used as a predictor of future fracture risk.1 Fracture risk increases progressively as BMD decreases.1,2

Once a BMD figure is obtained, a T-score can then be identified. A T-score is a comparison of the patient’s BMD with the BMD of a healthy young adult.2

The WHO categories osteoporosis and osteopaenia as the following:

Osteopaenia 

▸ Mild osteopaenia is a T score of -1 to -1.49.4

▸ Moderate osteopaenia is a T score of -1.5 to -1.9.4

▸ Marked osteopaenia is a T score of -2 to -2.49.4

▸ Osteoporosis is a T score of -2.5 or lower, ie, -3.5.4

▸ Severe osteoporosis T score of below -2.5 with one or more fractures.2,6

Treatment

Non-pharmacological treatment

Patients should be advised to adjust any modifiable risk factors, such as reduce alcohol intake and stop smoking.

Patients should aim to reduce fracture risk factor by increasing dietary calcium and vitamin D, participate in regular weight-bearing exercise such as walking, and muscle-strengthening exercises.4

Fall prevention is extremely important for these patients — ensure home environments are safe and clutter-free, and appropriate footwear is recommended. 

Pharmacological treatment

The aim of treatment is to slow down or stop bone loss, increase bone density, prevent fractures and increase a person’s quality of life.4

Calcium and vitamin D should be recommended to all patients, unless contraindicated.4 Some evidence suggests daily calcium intake in excess of 1,200mg may increase risk of kidney stones, cardiovascular disease and stroke, therefore calculation of daily intake, including from dietary sources, is sometimes recommended.2

Bisphosphonates work by inducing apoptosis of osteoclasts, therefore inhibiting bone resorption and decreasing risk of fractures.4 

There are many different formulations of bisphosphonates available in daily, weekly or monthly oral formulations and three-monthly or yearly IV formulations. Some bisphosphonates come in combinations with vitamin D. Alendronate, risedronate, ibandronate and zoledronic acid are examples of bisphosphonates.3

Counselling points for oral bisphosphonates include:2,3

▸ Should be taken after an overnight fast, first thing in the morning.

▸ Take at least 30 minutes before food or drink (other than water).

▸ Take at least 30 minutes before other medicinal products or supplements.

▸ Should be swallowed with a full glass of water (approximately 200ml).

▸ Patient must take the medication standing upright or sitting upright and patients should not lie down for at least 30 minutes after taking the medication.

Bisphosphonate treatment should be reviewed after five years, and after three years for zoledronic acid.3

Limitations to bisphosphonate therapy include: Severe renal impairment (crcl below 30-to-35ml/min), hypocalcaemia, oesophageal abnormalities, hiatus hernia, and gastritis.

Osteonecrosis of the jaw is a risk factor for bisphosphonate therapy but is a greater risk for IV bisphosphonates in the treatment of cancer. Risk factors for developing osteonecrosis of the jaw should be considered, including : Potency of bisphosphonate; route of administration; cumulative dose; duration; and history of dental disease.3

Denosumab is a monoclonal antibody that binds to the receptor on the osteoclast surface, which inhibits the maturation of the osteoclast, therefore protecting the bone from degradation, preventing bone loss and osteoporosis.2 

It is given as a six-monthly subcutaneous injection (Prolia) and considered useful for patients unable to tolerate bisphosphonates.3

Hypocalcaemia is a risk for patients treated with Denosumab, therefore vitamin D deficiency should be explored prior to treatment. A 50,000-to-100,000 unit oral loading dose of vitamin D should be advised for those with vitamin D deficiency prior to Denosumab therapy and adequate intake of calcium and vitamin D is important.2 Calcium level tests should be conducted prior to each Denosumab dose and within two weeks of initial dose to patients predisposed to hypocalcaemia.2

HRT3 — some HRTs comprising oestrogen or oestrogen plus progestogen are approved for prevention of osteoporosis in postmenopausal women and have been shown to reduce fractures with low bone density. However, the increased VTE risk and contraindication in breast cancer means it is restricted to younger postmenopausal women.2,4

Teriparatide,3 which is recombinant human parathyroid hormone (PTH) 1-34, stimulates osteoblastic activity.2 It is given as a subcut injection 20µg/day for 24 months and the course cannot be repeated.3 They are recommended for those with severe osteoporosis. Bone mineral content is lost quickly on cessation of therapy and therefore it is important to commence an antiresorptive agent when stopping therapy.5

Selective oestrogen — receptor modulators (SERMs), ie, raloxifene, are medications that exhibit oestrogen receptor agonist activity and maintain bone density and reduce fracture rates.4 Raloxifene is taken as a 60mg oral tablet daily. It has some limitations to use, as it is contraindicated in women of child-bearing potential, history of VTE, hepatic and severe renal impairment.2

Calcitriol is the active form of vitamin D and can be used for treatment of established postmenopausal osteoporosis at a dose of 0.25 nanograms twice daily. It inhibits bone resorption and reduces fracture risk.4

Strontium ranelate reduces bone resorption, prevents bone loss and increases bone formation and BMD through formation of new, normal, strong bone. It comes as a 2g sachet, which is taken daily with water. Calcium-containing products must be avoided two hours before and after dosing due to the interaction with calcium.4

References on request.