Interventions

Five interventions will be considered within this assessment: alendronic acid, risedronic acid, oral ibandronic acid, i.v. ibandronic acid and zoledronic acid. These interventions are described in detail in Chapter 1, Description of technology under assessment.

Populations (including subgroups)

The assessment considers the following populations:

1. all women aged ≥ 65 years and men aged ≥ 75 years
2. women aged ≤ 64 years and men aged ≤ 74 years in the presence of risk factors, for example previous fragility fracture; current use or frequent recent use of oral or systemic glucocorticoids; history of falls; family history of hip fracture; other causes of secondary osteoporosis; low BMI (< 18.5 kg/m²); smoking; alcohol intake of > 14 units per week in women or > 21 units per week in men
3. women aged 64 years and men aged ≤ 74 years with low BMD (a T-score of –1 SD or more below the young adult mean).

An evaluation of the interventions in the following populations is outside the appraisal scope and will not be considered in this assessment:

• women aged ≤ 64 years without a risk factor [see Populations (including subgroups)]
• men aged ≤ 74 years without a risk factor [see Populations (including subgroups)].

Relevant comparators

Bisphosphonates (alendronic acid, risedronic acid, oral ibandronic acid, i.v. ibandronic acid and zoledronic acid) may be compared with each other or with a non-active agent, for example placebo.

Other bisphosphonates (e.g. etidronic acid) and other active agents (e.g. raloxifene, strontium ranelate and teriparatide) will not be considered as comparators in this assessment.

Etidronic acid is not included as a comparator as it has been discontinued by the manufacturer in the UK. Non-bisphosphonates licensed for the prevention of fragility fractures in women and men will be considered in a separate multiple technology appraisal (MTA).

Outcomes

The outcome measures to be considered included:

• fragility fracture (fractures that result from mechanical forces that would not ordinarily result in fracture)
  • hip fracture
  • vertebral fracture (where data allow, clinical/symptomatic fractures will be reported separately from morphometric/radiographic fractures, with the latter being defined as those resulting in a ≥ 20% reduction in vertebral height)
  • all non-vertebral fracture
  • wrist fracture
  • proximal humerus fracture
  • fragility fracture at other sites
• BMD at the femoral neck assessed by DXA
• mortality
  • all cause
  • mortality following hip fracture
  • mortality following vertebral fracture
  • mortality following fracture at site other than hip or vertebral
• adverse effects of treatment including but not limited to
  • upper GI symptoms
  • osteonecrosis of the jaw
  • hypocalcaemia
  • bone pain (not associated with influenza-type symptoms)
  • atypical femoral fractures
  • influenza-like symptoms including bone pain, myalgia, arthralgia, fever and rigors
  • conjunctivitis
  • atrial fibrillation
  • stroke
• continuance (or persistence; proportion of people still on treatment at the end of a given period) and concordance (or compliance; proportion of prescribed doses taken during a given period)
• health-related quality of life (HRQoL)
• health-care resource use, for example hospitalisation, entry into long-term residential care.

Key issues

An evaluation of the interventions in the following populations is outside the appraisal scope and will not be considered in this assessment:

• women aged ≤ 64 years without a risk factor [see Populations (including subgroups)]
• men aged ≤ 74 years without a risk factor [see Populations (including subgroups)].