Title: Romosozumab for treating severe osteoporosis [ID3936]
Funder: Department of Health and Social Care

Abstract: Osteoporosis is a progressive skeletal disorder which is characterised by low bone mass and deterioration of the structure of the bone, leading to an increase in bone fragility and risk of fracture._x000D_ _x000D_ 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 osteoporosis.[1] Osteoporosis can also be caused by the long-term systemic use of corticosteroids._x000D_ _x000D_ 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._x000D_ _x000D_ Currently, related NICE guidance includes:_x000D_ _x000D_ • NICE clinical guideline 146, ‘Osteoporosis: assessing the risk of fragility fracture’, which recommends:_x000D_ o considering the assessment of fracture risk in all women aged 65 years and over and all men aged 75 years and over_x000D_ 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_x000D_ 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)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 FRAX or QFracture.[3],[4]_x000D_ _x000D_ • 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 clinical 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._x000D_ _x000D_ • NICE technology appraisal 204, which recommends denosumab:_x000D_ 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 cannot take alendronate and either risedronate or etidronate_x000D_ o for the secondary prevention of osteoporotic fragility fractures in postmenopausal women at increased risk of fractures who cannot take alendronate and either risedronate or etidronate._x000D_ _x000D_ • NICE technology appraisal 161, which recommends raloxifene, strontium ranelate (currently discontinued) and teriparatide at specified fracture risks defined by age, T-score and either number of independent clinical risk factors for fracture (raloxifene), or number of fractures (teriparatide). These recommendations are for women who have already sustained a fracture and who cannot take alendronate or risedronate._x000D_ _x000D_ References_x000D_ 1. Age UK (2020) Osteoporosis. Accessed February 2021_x000D_ 2. Compston J et al. (2017) UK clinical guideline for the prevention and treatment of osteoporosis. Archives of Osteoporosis 12(1): 43_x000D_ 3. FRAX, the World Health Organisation (WHO) fracture assessment tool, is available from https://www.sheffield.ac.uk/FRAX/. It can be used for people aged between 40 and 90 years, either with or without BMD values, as specified._x000D_ 4. QFracture is available from https://qfracture.org/. It can be used for people aged between 30 and 84 years. BMD values cannot be incorporated into the risk algorithm.

Lay abstract: To appraise the clinical and cost effectiveness of romosozumab within its marketing authorisation for treating severe osteoporosis in postmenopausal women at high risk of fracture.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL