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Boning – up on Osteoprosis

By Irish Pharmacist - 20th Sep 2021

A clinical overview of the causes, symtoms and treatment of the debilitating condition osteoporosis.

Osteoporosis literally means ‘porous bones’. It is a condition where bones lose density, causing them to become weak and more likely to fracture. Approximately 50 per cent of women and 20 per cent of men aged over 50 will experience a fracture due to osteoporosis. According to the Osteoporosis Society of Ireland, it is estimated that
300,000 people in Ireland have osteoporosis. Osteoporosis can affect all age groups, but it is most common
in postmenopausal women. Having osteoporosis does not automatically mean that bones will fracture; it just
means that it is more likely. Osteoporosis is a bigger cause of disability than common non-communicable
diseases such as Parkinson’s disease, rheumatoid arthritis, and breast cancer.

Symptoms

Osteoporosis may have no symptoms initially, and patients may be unaware of any problems until they
fracture a bone or start to lose height. Symptoms can include:

  • Sudden, severe episodes of upper, middle, or lower back pain.
  • Loss of height (greater than 2cm).
  • Development of a hump on the back or a change in body shape, for example, the rib cage may rest on pelvic rim, or a pot belly developos.

It is estimated

that 300,000 people

in Ireland have

osteoporosis

Diagnosis

Osteoporosis is usually diagnosed in hospital, often after a fall or a bone fracture. Bone density is measured
using a dual-energy x-ray absorptiometry (DEXA) scanner. Osteoporosis is diagnosed when bone density is found
to be significantly lower than average. DEXA scans are painless, take 10-to20 minutes and are the gold standard
for the diagnosis of osteoporosis. The results of the scan will be made available immediately or very soon
after, depending on where it is done. Scan results will be given in the form of a T-score. A T-score value greater
than -1 shows that bone density level is normal and there is no osteoporosis. A T-score value of between -1 and -2.5 indicates osteopenia. This is the early stage of osteoporosis and is a warning that a patient must start taking care of their bones. A T-score of below -2.5, meanwhile, indicates osteoporosis.

There is no comprehensive osteoporosis screening programme in Ireland. People generally only get a
DEXA when referred by their GP. The average waiting time tvo get a DEXA scan in 2008 for public patients was
20 weeks but that has likely increased due to the pandemic.15 Private patients can get a scan upon request in private facilities. The website of the Osteoporosis Society of Ireland has a comprehensive list of all locations in Ireland where DEXA scans are performed. It lists DEXA scan locations on a county-by-county basis and includes both private and public hospitals and clinics. The Osteoporosis Society website details all locations in Ireland.

Causes

Healthy bone consists of a strong mesh made of protein and minerals (particularly calcium). This mesh is living tissue that is constantly being renewed by two types of cells. One type builds up new bone (osteoblast cells), and the other breaks down old bone (osteoclastcells). Up to our mid-20s, our skeleton is strengthened, but from our 40s onwards, our bones gradually lose their density as a natural part of ageing.
There is a genetic influence on osteoporosis, so women with family members with the condition are more at risk.
However, other factors increase the risk of osteoporosis. Oestrogen protects women from osteoporosis from puberty until the menopause. After menopause, the breakdown of bone is quicker in women, as the
protective effect of oestrogen on the bones is gone.

The following can increase the risk of osteoporosis:

  • An early menopause (before the age of 45)
  • A hysterectomy before the age of 45 (especially if both ovaries are removed)
  • Excessive exercising — this can reduce hormone levels and as a result, periods may stop for a prolonged time.


Other factors include:

  • Age — the risk increases with age.
  • Race — Caucasian or Asian races are at greater risk than African-Caribbean
  • Gender — women have smaller bones than men
  • A family history of osteoporosis, particularly a history of hip fracture in a parent
  • A previous fragility fracture (fracturing a bone after only a minor accident).
  • Long-term immobility (ie, confined to bed)
  • A very low body mass index
  • Excessive alcohol consumption or smoking
  • Low levels of vitamin D or dietary calcium

Some medications and disorders can increase risk, including:

  • Long-term use of corticosteroids.
  • Long-term use of heparin
  • Aromatase inhibitors (for breast cancer treatment).
  • Overactive thyroid disorders.
  • Rheumatoid arthritis.
  • Digestive disorders that affect nutrient absorption, such as Crohn’s disease, chronic liver disease, or coeliac disease.

After menopause,

the breakdown of bone

is quicker in women

Causes in premenopausal women

Oestrogen generally prevents osteoporosis in premenopausal women. However,
there are certain medical conditions and medications which reduce oestrogen leveland hence cause early-onset osteoporosis.

Examples include:

  • Hypogonadotropic hypogonadismdue to low weight, eating disorders, excessive exercise, hyperprolactinemia, and hypopituitarism.
  • Hyperrgonadotropic hypogonadism (premature ovarian failure) is associated with bone loss if oestrogen is not replaced. Women with Turner syndrome (condition which occurs in less than one-in-2,500 due to abnormal X chromosome) may have an additional selective reduction in bone mineral density that is independent of oestrogen exposure
  • In premenopausal women with breast cancer, chemotherapy often results in premature ovarian failure, and as a result, oestrogen deficiency and bone loss.

Drugs that may be associated with bone loss in premenopausal women include glucocorticoids, anticonvulsants, ie, phenytoin, antidepressants, ie, lithium, and anticoagulants, ie, warfarin and heparin.

Non – Pharmacological Management

Non-pharmacological management includes prevention of falls and modification of risk factors including diet, smoking and excessive alcohol intake. Important measures aimed at preventing falls include attention to modifiable factors, including checking eyesight, exercise, reduced consumption of medication that alters alertness and balance, and improvement of the home environment. There is controversy on the use of hip protectors to prevent fractures, with recent evidence casting doubt on this preventive measure.

Attention to diet is important, because there is a high prevalence of calcium and
vitamin D insufficiency in the elderly, particularly those with chronic conditions. Calcium is necessary for maintaining bone health and vitamin D enhances the absorption of calcium. A diet with adequate calcium (>1,200mg daily) and vitamin D (800IU daily) is recommended for those with risk factors

Adults over 50 years often only consume 700mg calcium daily, so the use of supplements, including fortified food products, may be required. Evidence for the use of calcium and vitamin D supplements
to maintain optimum bone density in healthy adults with normal dietary intake is limited.4,5 However, a systematic review found that the ingestion of calcium or calcium with vitamin D reduced osteoporotic fractures in men and women over 50 years by 12 per cent.
They should be considered for patients in nursing/residential homes and the house-bound elderly. Immobility
is a major cause of bone loss.

Self – Help

Osteoporosis patients need to be careful of vigorous, high-impact exercise; however, being active improves balance, co-ordination and increases muscle strength, so reduces risk of falls and bone fractures Beneficial exercise includes swimming, gardening, walking and golf. Eating a diet rich in calcium is important for maintaining healthy bones. Dairy products and green-leafed vegetables are good sources of calcium. There is a misconception that low- or non-fat versions of dairy products have less calcium than full-fat versions, but this is not the case. People with an intolerance of dairy can as an alternative drink orange, grapefruit, and apple juice, which are calcium-fortified and have just as much calcium as milk.

The body also needs vitamin D to absorb calcium properly. Examples of food high in vitamin D include cod liver oil, oily fish such as mackerel, sardines and herrings, margarine, and egg yolks. It is also made by the skin when exposed to sunlight. The National Osteoporosis Society recommends about 20 minutes of sun exposure to the face and arms, every day during the summer, to provide enough vitamin D for the year. Avoid fizzy drinks and reduce caffeine, salt, or animal protein, as these can affect the balance of calcium in the body.

How much vitamin D is needed to prevent fractures?

Research has found that a daily supplement of 700 to 1,000IU of vitamin D reduces the risk of fractures from falls among older people by 19 per cent. In fact, the British Medical Journal shows that a dose of less than 700IU per day has no effect in reducing fractures.

Risk of Osteoporosis from corticosteroids

Patients on corticosteroids require preventive treatment for osteoporosis if the patient is starting oral corticosteroids and is likely to be on these for at least three months. More than three or four courses
of corticosteroids taken in the previous 12 months is equivalent to more than three months of continuous treatment. Evidence supports the use of bisphosphonates as a first-line treatment.

Physiotherapy falls

Many physiotherapy departments in Ireland have a falls prevention programme that GPs or hospital consultants
can refer patient to. Criteria for referral to a physiotherapy falls prevention programme include reduced mobility, history of falls, fear of falling. The programme is often based on the OTAGO exercise programme and aims
to strengthen muscles, thus preventing falls and reducing the risk of fracture if the patient does fall.

Hse Falls Prevention Policy

The following is the HSE falls prevention policy outlined in the HSE’s 2008 fall prevention report. Older patients should be asked these questions a minimum of once a year:

  • Have you fallen during the past year? If yes, did you fall more than once?
  • Have you any problems with your balance?
  • Are you afraid of falling?

Older persons who have had a single explained fall should be tested for gait and balance annually. This test is more important if they:

  • Have recurrent falls (two or more in the last year).
  • Had an unexplained fall.
  • Have problems with gait and balance.
  • Have a fear of falling.

The HSE states in its report the following risk factors and interventions that have been shown to reduce falls and should be included in multifactorial assessment and intervention:

  • Individualised exercise programme that includes a combination of resistance training, gait, balance, and co-ordination training.
  • Medication review and withdrawal of psychotropic and other medications.
  • Home environment assessment and modification by health professional.
  • Managing postural hypotension.
  • Vision assessment and referral for intervention
  • Assessment for vitamin D deficiency and insufficiency and treated if identified.
  • Identification of foot problems and appropriate treatment.
  • Behavioural modification and educational programmes should be considered. The following is a recommendation for residential long-stay care settings in the 2008 HSE Fall prevention report.
  • All residential care settings should have a fall prevention policy and be resourced to implement it.
  • All residents should receive a Fall Risk Assessment annually. A Fall Risk Assessment should also take place on admission and when health status changes occur.
  • Falls in residential care and nursing care homes should be recorded on a register. Each fall should be critically analysed for corrective action.

The fall prevention procedures of residential care homes are assessed in all Health Information and Quality Authority (HIQA) inspections.

Medication

Bisphosphonates. Examples include alendronic acid, risedronic acid, and ibandronic acid. They work by slowing down bone loss. They are taken once weekly, but ibandronic acid is taken once a month. They can reduce the frequency of fractures by 50 per cent. Bisphosphonates have been used in trial extensions for up to 10 years, which suggests that bone quality remains normal and that reductions in fracture risk are sustained for as long as treatment continues. However, it is important that it is reviewed every two years. There is no difference in the efficacy or safety profiles of bisphosphonates in patients aged under 65 and over 65. The oral bioavailability of bisphosphonates is low and is impaired by food. Oral formulations must be taken fasting, sitting upright with a full glass of water, followed by no food for up to one hour. This is to reduce the gastrointestinal effects experienced by patients. Compliance with treatment is a problem, particularly in view of these requirements.

The most common side-effects are gastrointestinal, including non-ulcer dyspepsia, oesophagitis, oesophageal strictures (narrowing of oesophagus), gastric and duodenal ulcers. Bisphosphonates are contraindicated in the presence of abnormalities of the oesophagus, and hypocalcaemia. There have been reports of osteonecrosis of the jaw (ONJ) reported with their use, particularly with IV formulations given in high doses for metastatic bone disease.11-13 ONJ is a condition where the jaw breaks. The prevalence of ONJ with bisphosphonates has been estimated to be about one-in-100,000 patient-years, which is similar to the prevalence in the overall population. Alendronates in tablet form should not be crushed as this increases risk of esophageal irritation. For patients
with slow swallow, alendronic acid is available in a 70mg/100ml strength and does not cause esophageal irritation; however the same precautions, such as sitting upright after taking and not eating for an hour after taking, still holds true for the liquid version.

Parathyroid hormone peptides, ie, teriparatide (Movymia). It works through the fact that it is very similar to parathyroid hormone; this hormone helps to regulate calcium levels and the activity of cells involved in bone formation. It is a subcutaneous injection (usually into side of stomach) and one injection is used daily. Trails show it reduces fractures by average of 41 per cent. It is only used if a patient cannot tolerate other treatments.

The most common adverse effects are nausea, limb pain, headache, and dizziness. Contraindications include
severe renal impairment, pre-existing hypercalcaemia and metabolic bone disease other than primary osteoporosis.

The selective oestrogen receptor modulator, ie, raloxifene. This is a synthetic hormone that mimics the effect of oestrogen on the bones. One tablet is taken daily. It reduces risk of fractures by approximately 47 per cent. There have been no studies to show the effect of raloxifene for more than five years. However, according to the manufacturer, there is no minimum time that raloxifene should be used once an improvement has been shown.
Raloxifene has been associated with an increased risk of venous thrombosis similar to that for hormone therapy,
and with exacerbation of hot flushes.

An increased risk of death due to stroke has been reported with raloxifene, and it should be used with caution in women with a history of, or risk factors for, stroke. It is contraindicated in women with child-bearing potential, history of venous thromboembolism (VTE) or unexplained uterine bleeding, hepatic impairment, and severe renal impairment. Hormone replacement therapy (HRT) relieves symptoms of the menopause by restoring hormones to a premenopausal level. HRT has also been shown to reduce osteoporosis. The use of HRT for osteoporosis prevention is restricted to short term use for younger post-menopausal women with menopausal symptoms at
high risk of fracture.

Strontium ranelate, ie, Protelos was a drug in sachet form that could be prescribed if a patient could not take
bisphosphonates. It stimulated new bone to grow and reduced bone loss. However, it was discontinued by the manufacturer in 2018 due to lack of demand.

Disclaimer: Brands mentioned in this article are meant as examples only and not meant as preference to other brands.

Contributor Information

Written and researched by
Eamonn Brady (MPSI), owner of
Whelehans Pharmacies in Mullingar
Tel 04493 34591 (Pearse St) or
04493 10266 (Clonmore). www.
whelehans.inet. Eamonn specialises in
the supply of medicines and training
needs of nursing homes throughout
Ireland. Email ebrady@whelehans.ie

References

  1. National Osteoporosis Guideline Group – Executive summary
    of Osteoporosis:
  2. Clinical guideline for prevention and treatment downloaded
    from http://www.shef.ac.uk/NOGG.
  3. Sawka A, Boulos P, Beattie K, Thabane L, Papaioannou A et al,
    Do hip protectors decrease the risk of hip fracture in institutional
    and community dwelling elderly? A systematic review and
    meta-analysis of randomized controlled trials. Osteoporosis
    International 2005; 16:1461-1474.
  4. Kiel D, Magaziner J, Zimmerman S, Ball L, et al, Efficacy of a
    hip protector to prevent hip fracture in nursing home residents.
    JAMA 2007; 298:413-422.
  5. Kanis JA, Burlet N, Cooper C, Delmas PD, Position Paper:
    European guidance for the diagnosis and management
    of osteoporosis in postmenopausal women. Osteoporosis
    International 2008; 19:399-428.
  6. Qaseem A et al, Pharmacologic Treatment of Low Bone
    Density or osteoporosis to prevent fractures: A clinical practice
    guideline from the American college of physicians. Ann Intern
    Med 2008; 149:197-213.
  7. Tang BMP, Eslick GD, Newson C, Smith C, Bensousson A, Use
    of supplementation or calcium in combination with vitamin D
    supplementation to prevent fractures and bone loss in people aged
    50 years and older: A meta-analysis. Lancet 2007; 370:657-66.
  8. Liberman UA, Long-term safety of bisphosphonate
    therapy for osteoporosis – a review of the evidence. Drugs
    Ageing 2006; 23: 289-298.
  9. Rabenda V et al, Adherence to bisphosphonate therapy
    and hip fracture risk in osteoporotic women. Osteoporosis Int
    2008; 19: 811-818.
    10.Chaiamnuay S, Saag K, postmenopausal osteoporosis.
    What have we learned since the introduction of
    bispohosphonates? Rev Endocrine Metabolic Disorder
    2006; 7:101-112.
  10. Lekkerkerker F et al, Adherence to treatment of osteoporosis:
    a need for study, Osteoporosis International 2007; 18:1311-1317.
  11. Edwards B et al, Pharmacovigilance and reporting oversight
    in US FDA fast-track process: Bisphosphonates and osteonecrosis
    of the jaw. Lancet Oncology 2008; 9:1166-1172.
  12. Bisphosphonates and osteonecrosis of the jaw in
    Drugs Safety Newsletter, Irish Medicines Board 2006; 23: 2.
    Available on www.imb.ie.
  13. Reid IR, Cundy T, Osteonecrosis of the jaw.
    Skeletal Radiolog 2009; 38:5-9
    15.SPC for Evista® (raloxifene) www.medicines.ie.
  14. HSE. Strategy to prevent falls and fractures in
    Ireland’s ageing population. Report of the National
    Steering Group on the Prevention of Falls in Older People
    and the Prevention and Management o


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