NOGG 2017: clinical guideline for the prevention and treatment of osteoporosis

National Osteoporosis Guideline Group


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Fracture risk assessment

  • The following clinical risk factors provide information on fracture risk independently of both age and bone mineral density (BMD):
    • low body mass index (BMI)
    • a history of a prior fracture at a site characteristic for osteoporosis
    • a parental history of hip fracture
    • smoking
    • glucocorticoids
    • excessive alcohol intake
    • rheumatoid arthritis
  • The International Osteoporosis Foundation and the World Health Organization recommend that risk of fracture should be expressed as an absolute risk, i.e. probability over a 10-year interval. The absolute risk of fracture depends upon age and life expectancy as well as the current relative risk. The period of 10 years covers the likely initial duration of treatment and the benefits that may continue if treatment is stopped
  • NICE has recommended the use of fracture risk assessment tools (FRAX or QFracture) in the assessment of patients:
    • FRAX and QFracture tools cannot be used interchangeably
    • NOGG intervention thresholds are based on FRAX probability
  • FRAX assessment does not take into account prior treatment or dose responses for several risk factors. Since it is not possible to model all such scenarios with the FRAX algorithm, these limitations should temper clinical judgment
  • Diagnostic assessment should include not only the assessment of BMD where indicated, but also the exclusion of diseases that mimic osteoporosis, elucidation of the cause of the osteoporosis, and the management of any associated morbidity
  • Recommendations for the routine investigation of patients with osteoporosis are shown in Table 1 (below)
  • Vertebral fracture assessment should be considered in postmenopausal women and older men if there is a history of ≥4 cm height loss, kyphosis, recent or current long-term oral glucocorticoid therapy, or a BMD T-score ≤-2.5. It should also be considered in individuals with a history of non-vertebral fracture after the age of 50 years
Table 1: Procedures proposed in the investigation of osteoporosis
ROUTINE OTHER PROCEDURES, IF INDICATED
  • History and physical examination
  • Blood cell count, sedimentation rate or C-reactive protein. Serum calcium, albumin, creatinine, phosphate, alkaline phosphatase and liver transaminases
  • Thyroid function tests
  • Bone densitometry (DXA)
  • Lateral radiographs of lumbar and thoracic spine or DXA-based lateral vertebral imaging
  • Serum protein immunoelectrophoresis and urinary Bence Jones proteins
  • Serum 25-hydroxyvitamin D
  • Plasma parathyroid hormone
  • Serum testosterone, sex hormone binding globulin, follicle stimulating hormone, luteinizing hormone
  • Serum prolactin
  • 24 hour urinary free cortisol/overnight dexamethasone suppression test
  • Endomysial and/or tissue transglutaminase antibodies
  • Isotope bone scan
  • Markers of bone turnover
  • Urinary calcium excretion
Other investigations, for example, bone biopsy and genetic testing for osteogenesis imperfecta, are largely restricted to specialist centres

Lifestyle measures

Calcium intake and vitamin D status

  • It is recommended that a daily calcium intake of between 700 and 1200 mg should be advised, if possible achieved through dietary intake
  • A simple dietary calcium intake calculator is available at www.cgem.ed.ac.uk/research/rheumatological/calcium-calculator
  • It is recommended that in postmenopausal women and men aged ≥50 years who are at increased risk of fracture, a daily dose of 800 IU of cholecalciferol should be advised
  • In postmenopausal women and older men receiving bone protective therapy for osteoporosis, it is recommended that calcium supplementation should also be given if the dietary intake is below 700 mg/day, and vitamin D supplementation with 800 IU/day of cholecalciferol considered in those at risk of/with evidence for vitamin D insufficiency

Physical activity

  • Regular weight-bearing exercise should be advised, tailored according to the individual patient
  • Physiotherapy is an important component of rehabilitation after fracture. Muscle strengthening and balance training exercise interventions may reduce falls by improving confidence and coordination as well as maintaining bone mass

Falls

  • Falls history should be obtained in patients with osteoporosis and further assessment and appropriate measures undertaken in those at risk

Pharmacological interventions

  • Recommendations concerning the major interventions for osteoporosis are based on high levels of evidence, and the grade of these recommendations is summarised in Table 2 (below)
  • The choice of agent is determined by the spectrum of anti-fracture effects across skeletal sites, side-effects, and cost
  • For more information about administration, contraindications and special precautions, please refer to the full guideline and the summary of product characteristics for individual drugs
Table 2: Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D
INTERVENTION VERTEBRAL FRACTURE NON-VERTEBRAL FRACTURE HIP FRACTURE
Alendronate A A A
Ibandronate A A* NAE
Risedronate A A A
Zoledronic acid A A A
Calcitriol A NAE NAE
Denosumab A A A
HRT A A A
Raloxifene A NAE NAE
Teriparatide A A NAE

*in subsets of patients only (post-hoc analysis)
A=grade A recommendation; NAE=not adequately evaluated; HRT: hormone replacement therapy.

Bisphosphonates

  • Alendronate is approved for:
    • treatment of postmenopausal osteoporosis (10 mg daily or 70 mg once weekly by mouth) and osteoporosis in men (10 mg daily)
    • prevention of postmenopausal osteoporosis (5 mg daily)
    • prevention and treatment of glucocorticoid-induced osteoporosis (5 mg daily or, in postmenopausal women not receiving hormone replacement therapy 10 mg daily)
  • Ibandronate 150 mg once monthly by mouth or 3 mg as an intravenous injection every 3 months is approved for the treatment of osteoporosis in postmenopausal women at increased risk of fracture
  • Risedronate 5 mg daily or 35 mg once weekly by mouth is approved for the treatment of postmenopausal osteoporosis, to reduce the risk of vertebral fracture and for the treatment of established postmenopausal osteoporosis, to reduce the risk of hip fractures. It is also indicated for the treatment of osteoporosis in men at high risk of fractures. Risedronate 5 mg daily is approved for the prevention of glucocorticoid-induced osteoporosis in postmenopausal women
  • Zoledronic acid 5 mg intravenously once yearly is approved for the treatment of osteoporosis in postmenopausal women and men at increased risk of fracture, including those with a recent low trauma fracture, and for the treatment of osteoporosis associated with long-term systemic glucocorticoid therapy in postmenopausal women and men
  • During bisphosphonate treatment, patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for possible atypical femur fracture

Denosumab

  • Denosumab is approved for the treatment of osteoporosis in postmenopausal women and men at increased risk of fractures, and for the treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. It is given as a subcutaneous injection of 60 mg once every 6 months
  • During treatment, patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an atypical femur fracture

Raloxifene

  • Raloxifene is approved for the treatment and prevention of osteoporosis in postmenopausal women
  • Raloxifene is taken orally as a single daily dose (60 mg) and may be taken at any time without regard to meals

Teriparatide

  • Teriparatide is approved for:
    • treatment of osteoporosis in postmenopausal women and in men at high risk of fracture
    • treatment of osteoporosis associated with systemic glucocorticoid therapy in women and men at increased risk of fracture
  • Teriparatide is given as a subcutaneous injection in a dose of 20 mcg/day. The duration of treatment is limited to 24 months

Calcitriol

  • Calcitriol (1, 25-dihydroxyvitamin D) is approved for the treatment of established postmenopausal osteoporosis in an oral dose of 0.25 mcg twice daily

Hormone replacement therapy

  • Hormone replacement therapy comprises a large number of formulations of oestrogen or oestrogen plus progestogen combinations, some of which are approved for the prevention of osteoporosis in postmenopausal women at high risk of fracture

Duration and monitoring of bisphosphonate therapy

  • Based on current evidence, continuation of bisphosphonate treatment beyond 3–5 years (3 years for zoledronic acid and 5 years for alendronate, ibandronate, and risedronate) can generally be recommended in the following situations:
    • age ≥75 years
    • previous history of a hip or vertebral fracture
    • occurrence of one or more low trauma fractures during treatment, after exclusion of poor adherence to treatment (for example less than 80% of treatment has been taken) and after causes of secondary osteoporosis have been excluded
    • current treatment with oral glucocorticoids ≥7.5 mg prednisolone/day or equivalent
  • If treatment is discontinued, fracture risk should be reassessed:
    • after a new fracture regardless of when this occurs
    • if no new fracture occurs, after 18 months to 3 years
  • Treatment review should be performed after 5 years of treatment with alendronate, risedronate, or ibandronate and after 3 years of treatment with zoledronic acid (see algorithm below)

Bisphosphonates: algorithm for long-term treatment monitoring

Glucocorticoid-induced osteoporosis

  • FRAX assumes an average dose of prednisolone (2.5–7.5 mg/day or its equivalent) and may underestimate fracture risk in patients taking higher doses and overestimate risk in those taking lower doses
  • For high doses of glucocorticoids, for example ≥15 mg prednisolone/day or its equivalent, greater upward adjustment of fracture probability may be required
  • Please refer to the full guideline for adjustment of FRAX estimates of fracture probability according to dose of prednisolone
  • In general, women age ≥70 years, or with a previous fragility fracture, or taking large doses of glucocorticoids (≥7.5 mg/prednisolone or equivalent/day) exceed the intervention threshold and should be considered for bone protective therapy
  • Because bone loss and increased fracture risk occur early after initiation of glucocorticoids, bone-protective treatment should be started at the onset of therapy in patients at increased risk of fracture
  • In individuals who are intolerant of these agents, or in whom they are contraindicated, zoledronic acid or teriparatide are appropriate options
  • Adequate calcium intake should be achieved through dietary intake if possible, with the use of supplements if necessary. An adequate vitamin D status should be maintained, using supplements if required. If glucocorticoid therapy is stopped, withdrawal of bone-protective therapy may be considered, but if glucocorticoids are continued long term, bone protection should be maintained in the majority of cases
  • Bone protective therapy may be appropriate in some premenopausal women and younger men, particularly in individuals with a previous history of fracture or receiving high doses of glucocorticoids

Osteoporosis in men

  • For the purposes of FRAX calculations, the BMD T-scores in men are calculated based on the female reference database
  • Secondary causes of osteoporosis are commonly found among men, so this population requires thorough investigation. Intervention thresholds for men are similar to those recommended for women
  • All men starting on androgen deprivation therapy should have their fracture risk assessed
  • Consider referring men with osteoporosis to specialist centres, particularly younger men or those with severe disease

Post-fracture care and Fracture Liaison Services

  • The Department of Health states that Fracture Liaison Services (FLS) should be provided for all patients sustaining a fragility fracture
  • FLS should be patient-centred, and integrated between primary and secondary care. Primary care physicians should follow-up patients at 4 and 12 months to review use of medications that increase the risk of falls and/or fracture, to ensure co-prescription of calcium and vitamin D with bone protective interventions and to monitor adherence to therapy

Case finding and intervention thresholds

Assessment and intervention thresholds in the UK for major osteoporotic fracture probability

  • The dotted line represents the intervention threshold while the assessment thresholds are shown within the amber area
algorithm-for-the-assessment-and-intervention-thresholds-for-major-osteoporotic-fracture
  • In the absence of a screening policy, a case-finding strategy is recommended where patients are identified because of a fragility fracture or by the presence of other clinical risk factors
  • Fracture risk should be assessed in postmenopausal women and men aged 50 years or more with the risk factors outlined below where assessment would influence management
  • Clinical risk factors considered in the FRAX assessment of fracture probability:
    • age
    • sex
    • low body mass index (≤19 kg/m2)
    • previous fragility fracture, including morphometric vertebral fracture
    • parental history of hip fracture
    • current glucocorticoid treatment (any dose, by mouth for 3 months or more)
    • current smoking status
    • alcohol intake of 3 or more units daily
    • secondary causes of osteoporosis including:
      • rheumatoid arthritis
      • type 1 diabetes
      • osteogenesis imperfecta in adults
      • long-standing untreated hyperthyroidism
      • hypogonadism/premature menopause (<45 years)
      • chronic malnutrition
      • chronic malabsorption
      • chronic liver disease
  • The intervention threshold up to age 70 years is set at a risk equivalent to that associated with a prior fracture, in line with current clinical practice and, therefore, rises with age. At age 70 years and above, fixed thresholds are applied (see figure above)

References

full guideline available from...
www.shef.ac.uk/NOGG

National Osteoporosis Guideline Group. NOGG 2017: Clinical guideline for the prevention and treatment of osteoporosis. March 2017


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