Osteoporosis

A systemic skeletal disease characterised by reduced bone mineral density and deterioration of bone microarchitecture, resulting in increased bone fragility and consequently elevated fracture risk.

It is an extremely common condition, particularly among postmenopausal women given the accelerated bone loss associated with oestrogen deficiency, though it also affects men and occurs secondary to a broad range of underlying conditions and medications.

The clinical significance of osteoporosis resides entirely in its associated fracture risk. Fracture prevention, rather than the biochemical or densitometric diagnosis in isolation, is therefore the fundamental, overarching goal of assessment and treatment.

Pathophysiology and risk factors

• Bone remodelling is a continuous, coupled cycle of osteoclastic bone resorption and osteoblastic bone formation.
• Peak bone mass is typically achieved in early adulthood, followed by a gradual, physiological age related decline.
• Postmenopausal oestrogen deficiency accelerates bone loss in women, because oestrogen restrains osteoclastic bone resorption.
• Primary osteoporosis comprises postmenopausal osteoporosis (the commonest form overall) and age related osteoporosis in older men and women.
• Secondary osteoporosis has an identifiable underlying cause or contributing condition:
  • glucocorticoid therapy, one of the commonest and most important secondary causes, with rapid bone loss, particularly in the first several months of treatment, and at doses lower than commonly appreciated
  • hypogonadism
  • hyperthyroidism
  • hyperparathyroidism
  • coeliac disease and other malabsorptive conditions
  • chronic kidney disease
  • prolonged immobility
• Identifying a secondary cause has direct treatment implications.
• Well established risk factors for osteoporotic fracture:
  • advancing age
  • female sex
  • low body mass index
  • a personal history of previous fragility fracture, one of the single strongest predictors of future fracture risk
  • a family history of hip fracture
  • current smoking
  • excess alcohol intake
  • prolonged glucocorticoid use
• Together these form the basis of the validated fracture risk assessment tools used in contemporary clinical practice.

• Osteoporosis is characteristically entirely asymptomatic until a fragility fracture occurs.
• The condition is therefore frequently not identified until that point, or through structured screening of appropriately identified higher risk individuals.
• Systematic risk assessment is needed; symptomatic presentation alone does not identify affected individuals before a first fracture.
• A fragility fracture occurs from a fall from standing height or less, or spontaneously without any identifiable significant trauma.
• It is the clinically significant consequence of osteoporosis and itself a direct indication for osteoporosis assessment and, generally, treatment.
• Characteristic sites are the hip, vertebral spine, wrist (distal radius) and proximal humerus.
• Vertebral compression fracture may present with acute back pain, but a substantial proportion occur silently, without a specific acute episode, and are identified incidentally on imaging performed for another indication.
• Multiple vertebral compression fractures over time produce progressive height loss and the characteristic thoracic kyphosis (dowager's hump) recognised in advanced, longstanding disease.
• Hip fracture is the most clinically significant osteoporotic fracture, given its substantial morbidity and mortality.
• A significant proportion of affected individuals experience permanent functional decline and loss of independence.
• There is a meaningful excess mortality risk in the year following the fracture.
• This underscores the clinical and public health significance of effective osteoporosis prevention and treatment.

• Dual energy x-ray absorptiometry (DXA) scanning is the standard, reference diagnostic investigation. It measures bone mineral density, typically at the hip and lumbar spine.
• The result is expressed as a T-score: the number of standard deviations the measured bone mineral density differs from the mean peak bone mass of a young, healthy adult reference population.
• A T-score of -2.5 or below at either site formally defines osteoporosis.
• A T-score between -1.0 and -2.5 defines osteopenia: reduced bone mineral density not meeting the formal osteoporosis threshold, though still associated with some degree of elevated fracture risk.
• Formal fracture risk assessment tools (including FRAX and similar validated instruments) combine clinical risk factors with, where available, bone mineral density measurement.
• They give an individualised estimate of absolute fracture risk over a defined future time period.
• This is generally more clinically useful and treatment-relevant than bone mineral density considered in isolation.
• A proportion of fragility fractures occur in individuals with bone mineral density in the osteopenic rather than the formally osteoporotic range, reflecting the independent contribution of clinical risk factors to overall fracture risk.
• Screening for secondary causes of osteoporosis is a standard component of diagnostic evaluation:
  • full blood count, calcium, phosphate, renal and liver function, and thyroid function
  • where clinically relevant, further targeted investigation, including coeliac serology, testosterone in men, and assessment for hyperparathyroidism or hypogonadism
• It is particularly relevant in younger patients, in men, and where the degree of bone density reduction appears disproportionate to age and the primary risk factor profile alone.
• Vertebral imaging (lateral spine radiography, or vertebral fracture assessment performed as an adjunct to standard DXA scanning) is appropriate where there is a history of significant height loss, back pain, or other clinical suspicion of vertebral compression fracture.
• These fractures are frequently silent and clinically inapparent, and are directly relevant to fracture risk assessment and treatment decision making.

• General, non-pharmacological measures are foundational and apply across the full range of osteoporosis severity:
  • adequate dietary calcium intake
  • correction of any identified vitamin D deficiency
  • regular weight-bearing exercise
  • smoking cessation
  • moderation of alcohol intake
  • falls risk assessment and falls prevention strategies, particularly in older, frailer individuals, given the direct relevance of falls to fracture risk beyond bone density alone
• Calcium and vitamin D supplementation is generally recommended for individuals with inadequate dietary intake or confirmed deficiency. It is a foundational adjunct to specific pharmacological treatment where indicated.
• Supplementation alone is generally insufficient for individuals with confirmed osteoporosis or significantly elevated fracture risk, who warrant specific, targeted pharmacological intervention.
• Bisphosphonates (alendronic acid, risedronate, or, for intravenous administration, zoledronic acid) are first line pharmacological treatment for the great majority of patients requiring specific osteoporosis treatment. They inhibit osteoclastic bone resorption.
• Oral bisphosphonates (alendronic acid or risedronate) are typically given weekly. Specific administration instructions are essential to optimise absorption and minimise the risk of oesophageal irritation: take on an empty stomach with a full glass of water, remaining upright for at least thirty minutes afterward.
• Intravenous zoledronic acid, given as an annual infusion, is an effective alternative, particularly for patients with gastrointestinal intolerance to oral bisphosphonates or concerns regarding treatment adherence.
• Denosumab is a monoclonal antibody targeting RANK ligand, thereby inhibiting osteoclast formation and activity. It is given as a subcutaneous injection every six months and is an effective alternative to bisphosphonate treatment.
• Discontinuation is associated with a recognised, significant risk of rebound bone loss and, in some cases, subsequent multiple vertebral fracture.
• This must be managed by transition to an alternative antiresorptive agent (typically a bisphosphonate) following discontinuation. It is an important, specific safety consideration in the ongoing management of any patient on denosumab.
• Anabolic agents are effective for severe osteoporosis or very high fracture risk:
  • teriparatide or abaloparatide: parathyroid hormone or parathyroid hormone related peptide analogues, given by daily subcutaneous injection
  • romosozumab: a sclerostin inhibitor, given by monthly subcutaneous injection
• They work through direct stimulation of new bone formation rather than the antiresorptive mechanism of the other agent classes.
• They are generally reserved for more severe disease or, in some cases, used as an initial treatment before transition to an antiresorptive agent to maintain the bone density gains achieved.
• Hormone replacement therapy provides effective bone protection in postmenopausal women. It may be appropriate, particularly in younger postmenopausal women where broader menopausal symptom management is also a treatment goal.
• It is not generally used as a primary, standalone osteoporosis treatment in older postmenopausal women, given the risk-benefit considerations of hormone therapy in this older population.
• Management of any identified secondary cause of osteoporosis is an essential, integral component of full management alongside specific osteoporosis pharmacological treatment.
• This includes optimisation of any underlying endocrine or gastrointestinal condition and, where clinically feasible, minimisation of glucocorticoid dose or duration where glucocorticoids are the secondary cause.
• Regular, structured follow up underpins longitudinal management of this common, significant condition:
  • periodic bone density reassessment, generally at intervals of one to three years according to the clinical context and treatment approach
  • ongoing monitoring of treatment adherence and relevant adverse effects
  • reassessment of overall fracture risk and continued treatment appropriateness over time
• Treatment duration and any "drug holiday" are addressed under specialist guidance. This is particularly relevant to prolonged bisphosphonate use, given the uncommon association of very prolonged treatment with atypical femoral fracture and osteonecrosis of the jaw.
• The overarching goal is fracture prevention rather than bone density optimisation as an end in itself.