Osteoporosis

• Osteoporosis


  A disease characterised by low bone mass and structural deterioration of bone tissue, with a consequent increase in bone fragility and fracture risk
• Osteoporosis


  • Asymptomatic and often remains undiagnosed until a fragility fracture occurs
  • Increases the risk of a fragility fracture
• Diagnosis of Osteoporosis


  1. Measure bone mineral density using dual-energy X-ray absorptiometry (DEXA)

  2. Osteoporosis is classified as a bone mineral density of 2.5 or more standard deviations below the mean peak bone mass

  3. Often diagnosed following a fracture
• Bone Remodelling


  Bones are constantly undergoing remodeling – this requires a balance between bone formation and resorption (breakdown)
• Cells involved in bone remodelling

  • Osteoblasts – create bone
  • Osteoclasts – break down bone and release calcium into the blood
• Factors regulating osteoblasts and osteoclasts

  • Oestrogen
  • Vitamin D
  • Parathyroid hormone
  • Calcitonin
• Ageing and bone loss

  1. Bone loss of 0.5-1% per year, starting around the age of 35-years-old

  2. Peak bone mass is achieved in the third decade

  3. Bone loss occurs as a result of increased bone breakdown by osteoclasts and decreased bone formation by osteoblasts

  4. Rate accelerates by as much as 10-fold during menopause, due to decreased oestrogen levels and increased osteoclast activity

  5. Rate of loss increases in older men due to decreased testosterone
• Risk factors for osteoporosis

  • Female sex
  • Increasing age
  • Menopause
  • Oral corticosteroids
  • Smoking
  • Alcohol
  • Previous fragility fracture
  • Rheumatological conditions, such as rheumatoid arthritis and other inflammatory arthropathies
  • Parental history of hip fracture
  • Body mass index of less than 18.5 kg/m2
• Role of oestrogen


  • Inhibits bone resorption by interfering with osteoblast derived factors that stimulate osteoclast activity
  • May also stimulate osteoblasts to create bone
  • Women have a lower peak bone mass than men, and when oestrogen levels fall during menopause, women lose bone mass rapidly
  • Bone mass in elderly men is also positively related to oestrogen levels
• Role of Vitamin D

  • Facilitates intestinal absorption of calcium
  • Stimulates osteoclasts leading to bone resorption
  • With parathyroid hormone maintains serum calcium levels
• Role of parathyroid hormone

  • Indirectly stimulates osteoclasts leading to bone resorption and increased serum calcium
  • Has a complicated mechanism – ratio of various different receptors and ligands determines the extent of bone resorption
• Role of calcitonin


  • Inhibits osteoclasts which indirectly leads to increased activity of osteoblasts
  • Reduces serum calcium
• Calcitonin was used for osteoporosis but no longer recommended for prophylaxis, or treatment of osteoporosis since the benefits are outweighed by a risk of malignancy when used long term
• Lifestyle advice


  1. Take regular exercise (tailored to the person) to improve muscle strength

  2. Eat a balanced diet as this may improve bone health

  3. Stop smoking, as it is a risk factor for fragility fracture

  4. Drink alcohol within recommended limits, as alcohol is a dose-dependent risk factor for fragility fracture
• Aim of pharmacological prophylaxis

  Reduce the risk of fractures occurring, by increasing bone mineral density and correcting deficiencies in calcium and vitamin D
• Bisphosphonates


  • Main pharmacological class used for prophylaxis and treatment of osteoporosis
  • Bind to hydroxyapatite crystals on the bone surface and rapidly inhibit the resorption of bone during remodeling
  • Mainly act by promoting apoptosis of osteoclasts
  • Also indirectly stimulate osteoblast activity
  • They therefore lead to an increase in bone strength
  • All bisphosphonates decrease risk of vertebral fractures
  • Alendronic acid and risedronate sodium also decrease the risk of non-vertebral (e.g. hip) fractures
• Examples of bisphosphonates


  • Alendronic acid
  • Ibandronic acid
  • Risedronate sodium
• Adverse events associated with bisphosphonates

  • Gastrointestinal issues including constipation, dyspepsia, pain and diarrhoea
  • Oesophageal reactions
  • Hypocalcaemia due to inhibition of bone resorption
• Rare bisphosphonate adverse events

  • Atypical femoral fractures
  • Osteonecrosis of the jaw
  • Osteonecrosis of the external auditory canal
• Bisphosphonate holiday


  • Due to the risk of rare but serious adverse events when using bisphosphonates, the need to continue treatment should be reassessed regularly
  • There is no consistent evidence of any further benefit or harm from continuing treatment with a bisphosphonate beyond three years and especially beyond 5 years in a patient with osteoporosis
  • Risk vs benefit should be regularly reassessed
  • High risk patients such as those over 75 years, those with a history of hip or vertebral fracture or patients, who have experienced a fracture whilst on treatment can continue bisphosphonates
• Calcium


  • Calcium supplements have been shown to reduce bone loss in post-menopausal women
  • There is no evidence that calcium alone reduces the incidence of fractures
  • If calcium is needed, a dose of 1000mg or more per day is required
  • Calcium should be used with caution if there is a history of renal stone formation
• Calcium and Vitamin D

  • Vitamin D deficiency is common, especially in the elderly
  • Calcium and Vitamin D supplementation is shown to decrease fracture risk, if dietary intake of calcium is inadequate
  • Lack of evidence to support the use of either calcium alone – the combination is important since Vitamin D promotes calcium absorption
  • If the patients calcium intake is adequate prescribe 400 units of vitamin D (without calcium) for people not exposed to much sunlight
  • If calcium intake is inadequate, prescribe 400 units of vitamin D with at least 1000 mg of calcium daily OR 800 units of vitamin D with at least 1000 mg of calcium daily for elderly patients who are housebound or living in a nursing home
• Hormone Replacement Therapy (HRT)


  • HRT can be considered for younger postmenopausal women to reduce the risk of fragility fractures and for the relief of menopausal symptoms
  • HRT is not considered for prophylaxis in women over 50-years-old due to the associated risks of long term use and a poor risk-benefit balance for osteoporosis in older women
  • HRT is effective at preventing vertebral fractures whilst treatment continues but bone loss will resume when treatment is stopped
  • HRT would therefore need to be continued lifelong, to maintain the beneficial effect which is not possible due to the increased cardiovascular and cancer risks associated with longer term use of HRT in older women
• Denosumab


  • Human monoclonal antibody
  • Inhibits osteoclast formation and activity via targeting a protein (RANKL), that stimulates osteoclast differentiation, and therefore decreases bone resorption
  • Licensed for men and postmenopausal women
  • Given S/C every 6 months
  • Requires supplementary calcium and Vitamin D
  • Regular blood test monitoring for calcium levels required throughout treatment
  • Expensive
  • Associated with bisphosphonate like side effects including atypical femoral fracture, osteonecrosis of the jaw and hypocalcaemia
• Raloxifene


  • Raloxifene is a selective oestrogen receptor modulator (SERM)
  • It has oestrogen like effects and increases osteoblast activity and reduces osteoclast activity thereby decreasing bone resorption
  • Raloxifene is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women who are unable to comply with the special instructions for the administration of bisphosphonates, or have a contraindication or are intolerant and have a combination of T-score, age and number of independent clinical risk factors for fracture
• Teriparatide


  • Teriparatide is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women and in men at increased risk of fractures who are unable to comply with the special instructions for the administration of bisphosphonates, or have a contraindication or are intolerant and have a combination of T-score, age and number of independent clinical risk factors for fracture
  • Active fragment of human parathyroid hormone
  • Stimulates the formation of new bone since intermittent exposure will actually increase the number and activity of osteoblasts
  • Daily S/C injection for up to 2 years
  • Restricted to maximum of 2 years use due to risk of osteosarcoma
  • Very expensive therefore only used under specialist care and reserved for the above patient group