SN2 SHORT NOTE 5M ★ High-yield

Define osteoporosis. Describe its causes, pathogenesis and diagnosis.

Pathology · 2nd Professional — Para-Clinical

Definition

Osteoporosis is a skeletal disorder characterised by reduced bone mass and microarchitectural deterioration, with normal mineralisation, leading to increased bone fragility and fracture. The bone is normal in quality but deficient in quantity.

Classification and Causes

Type	Causes
Primary — postmenopausal (type 1)	Oestrogen deficiency; affects trabecular bone predominantly; hence vertebral crush fractures and Colles fracture
Primary — senile (type 2)	Age-related; affects cortical and trabecular bone; hence femoral neck fractures
Secondary — endocrine	Corticosteroids (the commonest secondary cause), Cushing syndrome, hyperthyroidism, hyperparathyroidism, hypogonadism, diabetes
Secondary — nutritional	Calcium and vitamin D deficiency, malabsorption, anorexia nervosa, alcoholism
Secondary — other	Immobilisation, rheumatoid arthritis, myeloma, chronic kidney disease, heparin, anticonvulsants, osteogenesis imperfecta

Risk factors — mnemonic "shattered": Steroids, Hyperthyroidism and hyperparathyroidism, Alcohol and tobacco, Thin (low body mass index), Testosterone deficiency, Early menopause, Renal or liver failure, Erosive/inflammatory disease, Dietary calcium deficiency or malabsorption

Pathogenesis

Peak bone mass is reached at about 30 years, then declines → Bone is continuously remodelled by osteoclasts (resorption) and osteoblasts (formation) → oestrogen normally restrains osteoclasts by suppressing RANKL and raising osteoprotegerin → At the menopause, oestrogen falls → RANKL rises → osteoclast activity increases → Resorption exceeds formation → Trabeculae thin, perforate and lose connectivity — microarchitecture is lost, not merely mass → Fragility fracture after minimal trauma

CLINICAL PEARL

Osteoporosis is silent until the first fracture, which is exactly why it is dangerous. There is no pain from the bone loss itself. A vertebral crush fracture may be attributed to "old age" and a hip fracture treated as a fall — when the fracture is the disease presenting. Around a fifth of patients die within a year of a hip fracture, which is why case-finding matters.

Diagnosis

Serum calcium, phosphate and alkaline phosphatase are all normal — the biochemical signature, and what distinguishes it from osteomalacia and hyperparathyroidism
DEXA (dual-energy X-ray absorptiometry) is the standard: T-score at or below −2.5 = osteoporosis; −1 to −2.5 = osteopenia
Plain radiographs are insensitive — about 30 to 40% of bone mass must be lost before they show anything
Investigate for secondary causes in men, in premenopausal women, and where the picture is unusual — myeloma, hyperparathyroidism, thyrotoxicosis, coeliac disease and hypogonadism
FRAX estimates ten-year fracture probability from clinical factors, with or without a DEXA result

Applied Aspects

Prevention begins in adolescence by building peak bone mass — adequate calcium and vitamin D, and weight-bearing exercise
Bisphosphonates inhibit osteoclasts and are first-line; watch for oesophagitis, and rarely osteonecrosis of the jaw and atypical femoral fracture
Other agents — denosumab (an anti-RANKL antibody), teriparatide (recombinant PTH, which is anabolic), and selective oestrogen receptor modulators
Anyone on long-term corticosteroids needs bone protection from the start, not after a fracture — steroid-induced loss is fastest in the first months
Falls prevention matters as much as bone density — reviewing sedatives, correcting vision, treating postural hypotension and removing home hazards
Osteoporosis is under-recognised in India, occurs at a younger age than in the West, and coexists with widespread vitamin D deficiency — correcting the latter is cheap and should be routine

All questions in Endocrine, Bone & Breast Pathology

Every Pathology chapter →