Osteoporosis

Disease characterised by low bone density/strength and structural deterioration of bone tissue, with a consequent increase in bone fragility and predisposing patients to an increased risk of fracture.

An osteoporotic fracture is a low-impact fracture occurring as a consequence of osteoporosis.

NB A ‘low impact fracture’ is defined as a fracture caused by a fall from standing height or less.  A ‘major’ osteoporotic fracture is that of the spine, hip, forearm or proximal humerus (not femur/hip)

Pathophysiology

  • Bone is continually undergoing resorption and being remodeled by osteoclast and osteoblast cells, respectively.  Osteoporosis is a result of an imbalance of the activity of these cells.
  • Age
    • Peak bone mass occurs in the mid-20s and plateaus for about a decade (bone formation = resorption).  From then, bone loss occurs at about 0.3-0.5%/year due to a decrease in osteoblast cells relative to demand.  Trabecular (spongy) bone is lost more quickly due to higher cell turnover.
  • Oestrogen status
    • Oestrogen deficiency is the major cause of osteoporosis in post-menopausal women but can also be a major cause in men.  It promotes expression of RANKL (receptor activator of nuclear factor kappa B ligand) by osteoblasts and decreased expression of OPG (osteoprotegerin) which is important in the development of mature osteoclasts from precursor cells.  Thus the net result of oestrogen deficiency is increased osteoclastic activity, increasing bone loss to 3-5%/year for 5-10 years after the menopause.
  • The role of calcium, vitamin D and PTH

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    • Calcium and vit D deficiencies will both cause a rise in PTH, causing increased bone resorption to maintain calcium homeostasis.  If this is chronic, this can increase the risk of osteoporosis.
  • NB There can be other, secondary causes for osteoporosis (account for <5% in women but more in men):
    • Cancer (multiple myeloma); COPD (due to disorder +/- tobacco use +/- chronic steroid treatment); DRUGS (e.g. steroids; anticonvulsants; aromatase inhibitors; antihyperglycaemics); endocrine conditions (e.g. hyperparathyroidism; hypogonadism; diabetes); liver disease; malabsorption (e.g. crohn’s, coeliac)

Risk factors

NB Osteoporosis itself is asymptomatic but does significantly increase the risk of fragility fractures.  The risk of a fragility fracture, therefore, depends on the risk of osteoporosis (factors affecting bone mass or others) and the risk of falls/traumatic injury.

  • Risks that reduce BMD
    • Endocrine disease: diabetes; hyperthyroidism; hyperparathyroidism
    • Chronic GI conditions causing malabsorption: Crohn’s; UC; Coeliac
    • Chronic renal disease (low vit D metabolism)
    • Chronic liver disease
    • COPD (see above)
    • Immobility
    • Low BMI (<19kg/m²)
    • Age
    • Untreated premature menopause (<45 years old)
    • Low calcium diet
  • Risks that are independent of BMD
    • Age (partly)
    • Prolonged oral corticosteroid use (dose dependent) (see below)
    • Smoking and alcohol
    • Previous fragility fracture (particularly hip)
    • Rheumatoid arthritis/inflammatory arthropathy
    • Family history (of hip fracture/osteoporosis)
  • Other
    • SSRIs; PPIs; anticonvulsants
  • See also risks for falls

Presentation/Assessment

  • Who?
    • All women >65 and all men >75 years old
    • Anyone >50 with a risk factor for osteoporosis (above)
    • Anyone <50 with
      • current/frequent oral corticosteroid use
      • early menopause
      • previous osteoporotic/fragility fracture
    • Anyone <40 with
      • current or recent high dose oral steroid (>7.5mg prednisolone for >3 months) use
      • Previous fragility fracture(s)
  • How?
    • For people presenting with a fragility fracture:
      • Exclude other causes (metastatic disease, multiple myeloma) and exclude a potentially treatable cause for osteoporosis (e.g. hyperthyroidism)- particularly in low-risk individuals)
    • For anyone >40 with a predisposing risk factor
      • Use the FRAX® calculator to calculate risk and click NOGG-recommendations/guidelines thereafter to assess the need for lifestyle changes, DEXA scanning or active treatment

Investigations

  • Bloods- serum calcium/corrected calcium should be checked.  Also check for other causes in the blood work if there is a reason to (see above)- e.g. TFTs, FBC, LFTs, U&Es etc
  • DEXA scan
    • T-score (comparison to young normal reference mean) <-2.5 at the femoral neck is definitive of osteoporosis
      • between -1 and -2.5 is definitive of osteopenia
      • NB Severe Osteoporosis is a T-score <-2.5 + a fragility fracture
    • NB the Z-score (comparison to age-matched control mean) may be more useful in severe osteoporosis or in much older patients

Management

  • Low risk
    • Self-care and lifestyle advice
      • Replace deficient vitamin D and calcium
        • Many patients who are not outside at all during the day will most likely have some vit D deficiency.
        • Calcium intake may also be low (may be suggested by poor appetite/diet)
        • There are several options available: e.g. Accrete D3, Calceos, Natecal
      • Carry out a falls assessment
      • Advise to take regular exercise; stop smoking, stop drinking
  • Intermediate risk
    • Measure BMD using a DEXA scan then recalculate risk (if they are still intermediate, consider active treatment if they have a risk factor)
  • High-risk
    • You should prescribe HRT for a premature menopause
    • Offer bisphosphonates
      • Alendronate first line
      • Risedronate second line
    • Refer to a specialist if patients cannot tolerate these (common side effect include nausea and vomiting, muscle pain, mild gastritis; can rarely cause peptic ulcers, oesophageal problems and osteonecrosis of the mandible).  Contraindications for bisphosphanates include hypocalcaemia (patients must also be on calcium/vit D) and renal failure.
    • Secondary care treatments include strontium ranelate, raloxifine, denosumab and teriparatide.
      • There are various criteria (e.g. risk factors, T score cut offs) that should be fulfilled before using second line/specialist treatments

Guidelines for corticosteroid induced osteoporosis

  • Offer bisphosphonates if they are going to be on >30mg for >3 months; or >15mg for >3 months + one risk factor e.g. age >65
  • If there are no risk factors- consider performing DEXA scan and offer bisphosphonates if score <-1.5 (cf 2.5 of normal people)
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