CHAPTER 11 Eugene McCloskey1, Nicola Peel2, Jennifer Walsh1 and Richard Eastell1 1 Northern General Hospital; Academic Unit of Bone Metabolism, Mellanby Centre for bone research, Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK 2 Metabolic Bone Centre, Northern General Hospital (Sheffield Teaching Hospitals Foundation Trust), Sheffield, UK Bone undergoes a continual process of remodelling through the processes of osteoclastic resorption and osteoblastic formation in discrete remodelling units (Figure 11.1). About 10% of the adult skeleton remodels each year; remodelling maintains skeletal strength and plays a role in calcium homeostasis. The process is coupled so that resorption is followed by formation. Many systemic hormones and inflammatory mediators regulate osteoclastic resorption, and thus bone remodelling, through the generation of proresorptive RANK‐ligand (RANKL) and antiresorptive osteoprotegerin by osteocytes and osteoblasts. Regulatory pathways for osteoblast function are being elucidated; the Wnt pathway and its inhibitors (e.g. sclerostin) are of prime importance and provide novel targets for potential therapies. Figure 11.1 A schematic representation of the bone remodelling cycle in which osteoclastic bone resorption is followed by osteoblastic bone formation. Bone loss can occur as a result of increased resorption or decreased formation, relative to each other. Source: Courtesy of Richard Eastell Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue that results in a high risk of fragility fracture. With increasing age and in some disease states (Table 11.1), irreversible bone loss results from increased remodelling rates combined with an imbalance between the rates of resorption and formation; formation rates are particularly lowered during prolonged glucocorticoid therapy. Thinning and perforation of the trabecular plates, primarily in the early postmenopausal years, are followed by age‐related increases in cortical porosity in both women and men (Figure 11.2). Bone mineral density (BMD) measured by dual X‐ray absorptiometry (DXA) at the femoral neck, total hip or lumbar spine is used to diagnose osteoporosis; a T‐score ≤ –2.5 (i.e. 2.5 or more standard deviations below the young adult mean) is the WHO threshold for osteoporosis in postmenopausal women and men aged 50 years and older. BMD results in children and young adults who have not yet completed skeletal development are more appropriately interpreted by comparison to the mean value of the same age and gender (the Z‐score). Table 11.1 Relatively common causes of secondary osteoporosis Figure 11.2 The impact of osteoporosis on trabecular and cortical bone. Loss of bone mass is associated with structural deterioration in both bone envelopes, contributing to an even greater decrease in bone strength. Source: Zebaze et al. (2010). Reproduced with permission of Elsevier One in two women and one in five men will sustain a fracture related to osteoporosis by the age of 90 years; all fragility fractures in the elderly (e.g. women aged 75 years and older) should be regarded as osteoporotic once pathological fracture (e.g. metastatic disease) has been excluded. Recent estimates suggest that the cost of managing incident fractures in the UK is approximately £3.2 billion a year, rising to around £10 billion when loss of quality of life is included. While most fragility fractures are age related, an underlying cause (secondary osteoporosis) can be identified in up to 40% of cases of osteoporosis in women and 60% of cases in men (Table 11.1); appropriate investigations should be undertaken, especially if there is clinical suspicion. Individuals with a low‐trauma vertebral fracture or low BMD for age should certainly be investigated. In addition to a good clinical history, a small number of investigations can exclude the most common causes or alternative diagnoses, such as myeloma (Box 11.1). A history of prior low‐trauma fracture in adult life is a very important risk factor; it is important to remember that prior vertebral fractures may be asymptomatic and may not be identified without spinal imaging. Low radiation imaging of the thoracolumbar spine using DXA machines (vertebral morphometry) can now be undertaken in high‐risk groups as part of their routine assessment. DXA measurements of BMD are usually accurate and precise, though those reporting the scans should be aware of potential technical artefacts and limitations. Other measurement techniques, such as quantitative ultrasound, can predict osteoporotic fractures but appropriate intervention thresholds remain uncertain, as does their role in monitoring responses to treatment. The decision to undertake a DXA scan or to treat an individual is increasingly based on an assessment of absolute fracture risk, as recommended by NICE. Two fracture risk tools are available for use in the UK, QFracture and FRAX, with the latter having the advantage of taking BMD into account. The FRAX tool (www.shef.ac.uk/FRAX) estimates the probability of a major osteoporotic fracture (clinical vertebral, hip, wrist or proximal humerus) or a hip fracture in the next 10 years from a small number of clinical risk factors, with or without femoral neck BMD (Figure 11.3). For risk assessment, BMD measurements are best targeted to individuals whose risk of fracture lies at or near an intervention threshold, an approach endorsed by NICE, and implemented for FRAX by guidance from the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG) (Figure 11.4). Figure 11.3 A screenshot of the FRAX UK calculation page. The tool provides estimates of 10‐year probability of major fractures and hip fractures. The UK tool contains a link to transfer the result to the guidance page provided by the National Osteoporosis Guideline Group (see Figure 11.4). Source: Courtsey of Eugene McCloskey Figure 11.4 A screenshot of the NOGG guidance page. In the absence of a BMD result, the major fracture probability is plotted on a ‘traffic light’ graph as shown to recommend reassurance, BMD assessment or intervention if high risk. Source: Courtsey of Eugene McCloskey The ultimate goal of osteoporosis management is to reduce the future risk of fracture through patient education, falls prevention, lifestyle modification and pharmacological approaches. If access to DXA is limited, it may be appropriate to treat high‐risk individuals without DXA, such as elderly people with typical osteoporotic fractures or those who need high‐dose glucocorticoid therapy. It is important to remember that in secondary osteoporosis, treating the underlying cause often leads to at least partial recovery of bone mass. Groups such as the National Osteoporosis Society (www.nos.org.uk) provide excellent education and support for the patient and their carers. Two broad classes of treatments exist, namely antiresorptive and anabolic agents, and new agents in both classes are likely to be available in the next few years. Current treatments reduce the risk of vertebral fracture by 40–70%, hip fractures by 40% and other non‐vertebral fractures by 20–30%. Lifestyle advice with or without calcium and/or vitamin D supplementation should be regarded largely as adjuncts to osteoporosis treatments (Box 11.2). Vitamin D supplementation, alone or combined with calcium, may be of particular importance in frail elderly patients who are housebound or in residential care. Hypocalcaemia should be corrected by adequate intake of calcium and vitamin D before initiating other therapies, particularly intravenous bisphosphonates or subcutaneous denosumab. Poor adherence remains an issue with some therapies, so patient choice and ease of administration should be taken into account when making treatment choices.
Osteoporosis and Metabolic Bone Disease
Normal physiology of bone
Osteoporosis
Endocrine
Gastrointestinal
Rheumatological
Malignancy
Drugs
Thyrotoxicosis
Primary hyperparathyroidism
Cushing’s syndrome
Hypogonadism including anorexia nervosa
Diabetes (types 1 and 2)
Malabsorption syndrome, e.g. coeliac disease, partial gastrectomy
Inflammatory colitis
Liver disease, e.g. primary biliary cirrhosis
Rheumatoid arthritis
Ankylosing spondylitis
Multiple myeloma
Cancer treatment‐induced bone loss (see drugs)
Glucocorticoids
Anticonvulsants
Heparin
Aromatase inhibitors
Androgen deprivation therapy
Assessment of osteoporosis
Reducing fracture risk
Pharmacological agents
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
