26th January 2024

Background 

Osteoporosis is a skeletal disease characterised by low bone mass and abnormal bone architecture, which results in compromised bone strength, an increase in bone fragility and subsequent susceptibility to fracture. Osteoporotic (fragility) fractures are defined as those which result from mechanical forces, such as falling from standing height or less, or routine tasks, such as bending and lifting, that would not normally result in fractures. They are associated with a low BMD and most commonly occur at the spine, wrist, hip and shoulder.

Osteoporosis is defined by the World Health Organisation (WHO) as a bone mineral density (BMD) of 2.5 standard deviations below the BMD mean for young, healthy adults. BMD is measured by dual-energy X-ray absorptiometry (DEXA) at the femoral neck and reported as a T-Score. The four categories of T-scores are as follows:

• Normal: T-score ≥-1 (within 1 standard deviation of young, healthy white women)
• Osteopenia (low bone mass): T-score <-1 but >-2.5
• Osteoporosis: T-score of ≤-2.5
• Severe (or established) osteoporosis: T-score ≤-2.5 with presence of one or more fragility fractures)

Bone strength is not only determined by BMD but can also be associated with factors such as size and shape of the bone, bone turnover, quality of bone micro-architecture and bone mineralisation.

Osteoporosis itself is asymptomatic; therefore, the condition usually presents only after a bone fracture. The most common sites for fragility fractures are spine (vertebrae), hip (proximal femur) and wrist (distal radius); however, they may also occur in the arm, pelvis, ribs and other bones. Clinical signs and examination findings depend on the site of the fracture.

Epidemiology

Women are at greater risk of osteoporosis than men due to a decrease in oestrogen production after the menopause. It is estimated that more than 2 million women have osteoporosis in England and Wales. The prevalence of osteoporosis increases markedly with age, to more than 25% at 80 years in women. White men and women are predominantly affected, but people of any ethnicity can develop this condition. 1 in 3 women and 1 in 5 men are thought to suffer with an osteoporotic fracture in their lifetime.

Pathophysiology 

Osteoporosis results from an imbalance in the normal process of bone remodelling by osteoclasts and osteoclasts. Through the process of normal ageing, the breakdown of bone via osteoclasts increases and is not balanced by the formation of new bone by osteoblasts. This culminates in reduced BMD and changes in the composition, architecture, size and structure of the bone. The remodelling of bone is regulated by various cytokines, including interleukins 1, 6, and 11, colony-stimulating factors, and hormones such as parathyroid hormone, 1,25-dihydroxy vitamin D, calcitonin, and oestrogen. Factors such as tumour necrosis factor (TNF), receptor activator of nuclear factor- kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) contribute to the resorption of bone in postmenopausal osteoporosis. RANKL secreted by osteoblasts interacts with RANK receptors on osteoclasts to promote the formation, function and differentiation of osteoclasts, thereby triggering bone resorption. OPG is expressed by osteoblasts and plays a role in the inhibition of the activation of RANK.

Causes and risk factors

Osteoporosis manifests when there is inadequate peak bone mass and/or ongoing bone loss. Peak bone mass is achieved in early adulthood. It depends on genetics, sex hormone status, levels of physical activity and nutritional intake of calcium and vitamin D. The rate of bone loss is accelerated in women around the time of the menopause due to oestrogen deficiency, decreased testosterone in elderly men and hyperparathyroidism.

The risk of sustaining a fragility fracture is influenced by factors, including bone strength (determined by BMD), the individual patient’s risk of falls and the presence of certain risk factors. As the BMD decreases, the risk of fractures increases, but BMD alone cannot be used to predict fracture risk in the absence of consideration of other risk factors. The risk factors affecting bone strength can be subdivided into those that reduce BMD, those which do not reduce BMD and those with unestablished mechanisms as shown in the table below.

Table 4: Risk factors affecting bone strength

Adapted from Kumar and Clark’s Clinical Medicine. 2017 Kumar P, Clark ML. Kumar and Clark’s Clinical Medicine E-Book. Elsevier Health Sciences; 2012 Jun 4.

Falls are often multifactorial; however, some common risk factors are impaired vision, impaired gait, lower limb weakness, use of alcohol and drugs, and polypharmacy.

References 

• Johansen A, Harding K, Evans R, Stone M. Trauma in elderly people: what proportion of fractures are a consequence of bone fragility? Archives of gerontology and geriatrics. 2000 Feb 1;29(3):215-21.
• Wilkinson I, Wilkinson IB, Raine T, Wiles K, Goodhart A, Hall C, O’Neill H. Oxford handbook of clinical medicine. Oxford University Press; 2017.
• Kumar P, Clark ML. Kumar and Clark’s Clinical Medicine E-Book. Elsevier Health Sciences; 2012 Jun 4.
• Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocrine reviews. 2000 Apr 1;21(2):115-37.

• Conaghan PG, Dickson J, Grant RL. Care and management of osteoarthritis in adults: summary of NICE guidance. Bmj. 2008 Feb 28;336(7642):502-3.
• National Institute for Health and Care Excellence (Great Britain). Osteoporosis: assessing the risk of fragility fracture. National Institute for Health and Care Excellence (NICE); 2017
• Christodoulou C, Cooper C. What is osteoporosis? Postgraduate medical journal 2003 Mar 1;79(929):133-8.