Title: Non Bisphosphonates for treating Osteoporosis (review of TA 160/161/204) [ID901]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of abaloparatide, denosumab raloxifene, romosozumab and teriparatide, within their licensed indications, for the prevention of osteoporotic fragility fractures .

Lay abstract: Osteoporosis is a progressive skeletal disorder which is characterised by low bone mass and deterioration of the structure of bone tissue, leading to an increase in bone fragility and risk of fracture. Osteoporosis is asymptomatic and often remains undiagnosed in the absence of fracture. In the UK, it is estimated that around 3 million people have osteoporosis, which is defined as having a bone mineral density (BMD) that is 2.5 standard deviations or more below the average value for young healthy adults (usually referred to as a ‘T-score’ of -2.5 or lower). The prevalence of osteoporosis increases markedly with age. In women, decreased oestrogen levels after the menopause accelerate bone loss, increasing the risk of osteoporosis. Half of women and one-fifth of men over the age of 50 will break a bone, mostly as a result of low bone strength.1 Osteoporosis can also be caused by the long-term systemic use of corticosteroids. There are approximately 536,000 new fragility fractures in the UK per year.2 Osteoporotic fragility fractures occur most commonly in the hip, vertebrae and wrist. After a hip fracture, a high proportion of people are permanently unable to walk independently or to perform other activities of daily living and, consequently, many are unable to live independently. Vertebral fractures can be associated with curvature of the spine and height loss, and can result in chronic pain, breathing difficulties, gastrointestinal problems and difficulties in performing activities of daily living. Both hip and vertebral fractures are associated with increased mortality. Currently, related NICE guidance includes: • NICE clinical guideline 146, ‘Osteoporosis: assessing the risk of fragility fracture’, which recommends: o considering the assessment of fracture risk in all women aged 65 years and over and all men aged 75 years and over o considering the assessment of fracture risk in women aged under 65 years and men aged under 75 years in the presence of risk factors o not routinely assessing fracture risk in people aged under 50 years unless they have major risk factors (for example, current or frequent recent use of systemic corticosteroids, untreated premature menopause or previous fragility fracture) o estimating absolute fracture risk when assessing risk of fracture (for example, the predicted risk of major osteoporotic or hip fracture over 10 years, expressed as a percentage) using either FRAX3 or QFracture.4 See Appendix A for the full recommendations from NICE clinical guideline 146. • NICE technology appraisal 464, which recommends oral bisphosphonates (alendronic acid, ibandronic acid and risedronate sodium) and intravenous bisphosphonates (ibandronic acid and zoledronic acid) as options for treating osteoporosis in people who are eligible for risk assessment as defined in NICE's guideline 146 on osteoporosis, depending on the person’s risk of fragility fracture. However, the risk level at which oral bisphosphonates are cost effective is not a clinical intervention threshold. This technology appraisal guidance should be applied clinically in conjunction with the NICE quality standard 149 on osteoporosis that defines the clinical intervention thresholds. These thresholds are based on the NICE- accredited National Osteoporosis Guideline Group guideline. • NICE technology appraisal guidance 204, which recommends denosumab: o for the primary prevention of fragility fractures in postmenopausal women at specified fracture risks, defined by age, T-score and number of independent clinical risk factors for fracture, who have osteoporosis and who are unable to comply with the special instructions for administering alendronate and either risedronate or etidronate, or have an intolerance of, or a contraindication to, those treatments o for the secondary prevention of osteoporotic fragility fractures in postmenopausal women at increased risk of fractures who are unable to comply with the special instructions for administering alendronate and either risedronate or etidronate, or have an intolerance of, or a contraindication to, those treatments. • NICE technology appraisal guidance 161, which recommends raloxifene and strontium ranelate (currently discontinued), and teriparatide at specified fracture risks, defined by age, T-score and number of independent clinical risk factors for fracture, for women who have already sustained a fracture and who cannot take alendronate. Treatments for osteoporosis generally fall into 2 classes, bone-forming agents (abaloparatide, romosozumab and teriparatide) and anti-resorptive agents (bisphosphonates, denosumab and raloxifen) agents. Bone-forming agents are used for shorter durations of treatment, often in patients at very high risk of fracture, whereas anti-resorptive agents are used as long-term treatments sometimes after bone-forming agents. References 1 National Osteoporosis Society (2017) Available at http://www.nos.org.uk/page.aspx?pid=328. Accessed April 2018. 2 National Osteoporosis Guideline Group (2017) Clinical guideline for the prevention and treatment of osteoporosis. Accessed April 2018.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL