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Osteoporosis and Calcium Homeostasis

Must KnowApplied Basic SciencesthinKbox SBA

Definition

Osteoporosis is a skeletal disorder characterised by reduced bone strength and increased fracture risk. Bone strength reflects both bone mineral density and bone quality.

DXA

Dual-energy X-ray absorptiometry is the standard method for measuring bone mineral density at clinically relevant sites.

T-score

Compares the patient's bone mineral density with the young-adult reference mean.

In postmenopausal women and older men, a T-score of -2.5 or lower at an accepted site is diagnostic of osteoporosis in the appropriate clinical setting.

Z-score

Compares the patient with an age- and sex-matched reference population. It is particularly useful when assessing unexpectedly low bone mass in younger patients.

Limitations of DXA

Apparent bone density can be falsely increased by:

  • osteophytes
  • degenerative sclerosis
  • vertebral compression
  • calcification overlying the measured region

Always interpret the number alongside the image and clinical context.

Risk factors

  • increasing age
  • previous fragility fracture
  • low body weight
  • glucocorticoid exposure
  • smoking
  • excess alcohol
  • hypogonadism
  • malabsorption
  • endocrine disease
  • chronic inflammatory disease
  • immobility

FRAX

FRAX estimates 10-year fracture probability using clinical risk factors with or without femoral-neck bone mineral density. Treatment thresholds vary by country and guideline.

Calcium homeostasis

Parathyroid hormone

PTH raises extracellular calcium through effects on:

  • bone
  • kidney
  • activation of vitamin D

Vitamin D

Active vitamin D increases intestinal absorption of calcium and phosphate and is essential for normal mineralisation.

Kidney

The kidney regulates calcium and phosphate balance and activates vitamin D. Chronic kidney disease can cause secondary hyperparathyroidism and renal bone disease.

Treatment classes

Antiresorptive therapy

Reduces bone resorption. Examples include:

  • bisphosphonates
  • denosumab

Anabolic therapy

Stimulates bone formation. Examples include PTH-pathway agents and other anabolic treatments used in selected high-risk patients.

Choice depends on fracture risk, renal function, prior treatment, contraindications and local guidance.

Bisphosphonates

Bisphosphonates bind strongly to bone mineral and reduce osteoclast-mediated resorption.

Important adverse effects include:

  • gastrointestinal problems with oral preparations
  • acute-phase reaction after some intravenous doses
  • rare osteonecrosis of the jaw
  • rare atypical femoral fractures with prolonged exposure

Bisphosphonates bind to mineralised bone and are taken up by osteoclasts during resorption, reducing osteoclast activity and survival. Long-term treatment decisions should consider benefits, adherence and uncommon complications such as atypical femoral fracture and osteonecrosis of the jaw in relevant settings.

Secondary fracture prevention

A fragility fracture is an opportunity to:

  • assess osteoporosis
  • investigate secondary causes
  • optimise calcium and vitamin D when appropriate
  • address falls risk
  • initiate evidence-based bone protection when indicated

Bone mass and fracture risk

Osteoporosis is characterised by reduced bone strength and increased fragility-fracture risk. Bone strength depends on:

  • bone mineral density
  • microarchitecture
  • cortical thickness and porosity
  • trabecular connectivity
  • turnover
  • accumulated damage
  • geometry

A patient can therefore sustain a fragility fracture even when a single bone-density measurement does not appear profoundly abnormal.

Calcium regulation

Serum calcium is tightly regulated by parathyroid hormone, vitamin D and the skeleton-kidney-gut axis.

Parathyroid hormone increases serum calcium through effects on:

  • renal calcium conservation
  • phosphate excretion
  • activation of vitamin D
  • bone turnover through osteoblast-mediated signalling to osteoclast lineage cells

Vitamin D promotes intestinal calcium and phosphate absorption and supports normal mineralisation.

Vitamin D pathway

Vitamin D is obtained from skin synthesis and dietary sources. It is hydroxylated in the liver to 25-hydroxyvitamin D and then in the kidney to the active form, 1,25-dihydroxyvitamin D.

Deficiency can cause impaired mineralisation, secondary hyperparathyroidism and muscle weakness. Severe deficiency produces osteomalacia in adults and rickets in children.

Osteoporosis versus osteomalacia

Osteoporosis involves reduced quantity and altered quality of normally mineralised bone.

Osteomalacia is defective mineralisation of osteoid.

This distinction is important because both can present with fractures but have different biological abnormalities and treatment.

Bone turnover

Oestrogen deficiency increases bone resorption and is a major contributor to postmenopausal bone loss. Ageing also affects osteoblast function, calcium balance, muscle function and falls risk.

Secondary causes should be considered when the presentation is atypical, severe or occurs at a young age.

Treatment principles

Management is broader than prescribing a drug:

  • evaluate falls risk
  • ensure adequate calcium intake
  • correct vitamin D deficiency
  • encourage appropriate weight-bearing and resistance exercise
  • address smoking and excess alcohol
  • review medications
  • investigate secondary causes when indicated

Pharmacological agents may be antiresorptive or anabolic. Choice depends on fracture risk, previous fractures, renal function, contraindications and local guidance.

Fragility fracture pathway

A low-energy hip, vertebral, wrist or proximal humerus fracture should prompt secondary prevention. The orthopaedic episode is an opportunity to identify osteoporosis and reduce future fracture risk.

FRCS synthesis

Explain osteoporosis as a problem of bone strength and future fracture probability, not simply a low DXA number. Pair treatment of skeletal biology with falls prevention and rehabilitation.

Written/reviewed by Kishore Puthezhath

Professor of Orthopaedics and Consultant Paediatric Orthopaedic Surgeon

FRCS (Tr & Orth) revision resource

Reviewed: September 2026