Osteoporosis: Risk factors, diagnosis, and treatment

Osteoporosis meaning ‘porous bone’ is a progressive disease that occurs when the body loses bone mass and increases bone fragility and susceptibility to fractures. Osteoporosis affects up to 50 per cent of women and 25 per cent of males over the age of 50 years. An estimated 300,000 people in Ireland have osteoporosis.

In the general population bone mass increases through childhood, peaks in adolescence, remains relatively constant in early/late adulthood and declines in old age. The adult skeleton is continually re-modelling through bone resorption followed by bone formation. Osteoclasts are involved in bone resorption and osteoblasts are involved in bone formation.

The rate of re-modelling is affected by many factors including
sex hormones, vitamin D and parathyroid hormone. When balance is altered for various reasons this can then result in greater bone removal than replacement which leads to the development of osteoporosis.

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, eg, a simple trip.

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. In Ireland, €402 million per year is spent on treating a fall and fracture in the elderly. 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.

Risk factors

Some risk factors for osteoporosis include:

• Postmenopausal women – as women lose up to 30 per cent of their overall bone mass when they go through menopause.
• Men aged over 50 years.
• Low BMI.
• Cigarette smoking.
• Excess alcohol – alcohol intake and fracture risk is dose dependent.
• Lack of physical activity – especially at a young age when most bone is being formed.
• Vitamin D deficiency.
• Low calcium intake.
• Family history of fractures is considered a strong risk factor as approximately 80 per cent of bone mass is genetic.
• Rheumatoid arthritis and diabetes – some medical conditions which are linked with low bone mass density (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.
• Women whose period started later than the age of 15 years or had early menopause are at higher risk for bone loss due to irregularities in sex hormones.

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

• Patients taking long-term oral corticosteroids.
• Depo provera contraception is known to cause bone loss especially when started earlier in life.
• Chemotherapy.
• Some antiepileptic medications (eg, phenytoin) interfere with calcium absorption and the production of vitamin D.
• Proton pump inhibitors.
• The fracture risk assessment (FRAX) tool has been recommended by the World Health Organisation (WHO) to evaluate the fracture risk of
• patients.
• This tool computes the 10-year probability of hip fractures or major osteoporotic fracture. In the UK, NICE recommend the use of a risk assessment tool in all women over 65 years and males over 75 to aid identification of unknown osteoporosis.

Diagnosis

Osteoporosis can be diagnosed by the presence of fragility fractures, measurement of BMD or less commonly by bone biopsy. Early diagnosis is key to optimum results. Dual-energy x-ray absorptiometry (DXA) scans are the gold standard for diagnosing osteoporosis. A DXA scan applied to the femoral neck is the preferred site by the WHO and International Osteoporosis Foundation due to the higher predictive value for fracture risk.

The spine is not recommended as a suitable site for diagnosis of osteoporosis in older patients as there is a proportionally higher prevalence of degenerative changes which would inflate the BMD score, however, it is used as a site for assessing response to treatment.

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

Once a BMD figure is obtained, a T-score can then be identified. A T-score is a comparison of BMD with the BMD of a healthy young adult.

The WHO categories osteoporosis and osteopaenia as the following:

• Mild osteopaenia is a T-score of -1 to -1.49.
• Moderate osteopaenia is a T-score of -1.5 to -1.9.
• Marked osteopaenia is a T-score of -2 to -2.49.
• Osteoporosis is a T-score of -2.5 or lower, eg, -3.5.
• Severe osteoporosis is a T-score of below -2.5 with one or more fractures.

Treatment

Non-pharmacological treatment:

Patients should be advised to adjust any modifiable risk factors such as to reduce alcohol 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 exercise.

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.

Calcium and vitamin D should be recommended to all patients unless contraindicated. 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.

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

There are many different formulations of bisphosphonates available from 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.

Counselling points for oral bisphosphonates:

• 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. Limitations to bisphosphonate therapy includes: Severe renal impairment (crcl below 30-35ml/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.

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. It is given as a six-monthly subcutaneous injection (Prolia).

It is also considered useful for patients unable to tolerate bisphosphonates.
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 with vitamin D is important. Calcium levels should be checked prior to each denosumab dose and within two weeks of initial dose to patients predisposed to hypocalcaemia.

HRT – some HRT comprising of 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 venous thromboembolism (VTE) risk and contraindication in breast cancer means it is restricted to younger postmenopausal women
Teriparatide, which is recombinant human parathyroid hormone (PTH) 1-34, stimulates osteoblastic activity. It is given as a subcutaneous injection 20μg/day for 24 months and the course cannot be repeated.

It is recommended for those with severe osteoporosis. Bone mineral content is lost quickly on cessation of therapy and therefore it is important to commence an anti-resorptive agent when stopping therapy.

Selective oestrogen-receptor modulators (SERMs), eg, raloxifene, are medications that exhibit oestrogen receptor agonist activity and maintain bone density and reduce fracture rates. Raloxifene is taken as a 60mg oral tablet daily.

It has some limitations to use as it is contraindicated in women of childbearing potential, history of VTE, hepatic and severe renal impairment.

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.

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.

References on request

Protecting osteoporosis patients during Covid-19 by Priscilla Lynch

The key message of the recent 2020 Irish Osteoporosis Society (IOS) annual conference was continuation of care for osteoporosis patients during the Covid-19 pandemic and the importance of fracture prevention efforts.

Many patients and healthcare professionals themselves are not fully cognisant of the risks of ‘drug holidays’ for osteoporosis therapies, which anecdotally seem to have increased during the pandemic, the conference heard.

A number of speakers warned against taking drug holidays for the stronger osteoporosis therapies in particular, such as the human monoclonal antibody denosumab, which is used for the treatment of osteoporosis and treatment-induced bone loss. The six-monthly subcutaneous injection inhibits osteoclast bone resportion, thereby decreasing the release of calcium from bone into the blood stream, and is a very potent treatment but its effects can wear off very quickly if stopped suddenly, rapidly increasing fracture risks.

The conference heard powerful testimonies from a number of Irish female osteoporosis patients about their negative experiences of drug holidays (fractures, falls, pain and disability) and the impact of late diagnosis and inadequate osteoporosis treatment.

Speaking to the Medical Independent, IOS President Prof Moira O’Brien said she would never put one of her patients on a drug holiday, and voiced concern about osteoporosis patients “slipping through the cracks” during the Covid-19 pandemic. She called on all healthcare professionals to ensure that their patients continue to receive appropriate care and treatments for osteoporosis, and that suspected cases continue to be referred for DXA scans and full assessments.

High stress levels raise cortisol levels and cause bone loss. “This is very important to remember and very few people realise it,” Prof O’Brien said, noting that the pandemic has increased stress levels among the population.
The IOS helpline has received an increased number of calls in recent months from osteoporosis patients who report not attending their medical professionals for follow ups or to receive treatment and scans as they are frightened of getting Covid-19, and are thus increasing their fracture risks.

Prof O’Brien advised that the IOS website contains a number of useful tools and educational resources for both healthcare professionals and patients, and called on all healthcare professionals to refer their patients to the site,
www.irishosteoporosis.ie