Clinical overview
Osteoporosis is a systemic skeletal disorder characterised by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The operative concept is bone strength, and bone strength is the product of two things: bone density (how much mineralised bone there is) and bone quality (microarchitecture, turnover rate, mineralisation, the accumulation of microdamage, and collagen properties). Densitometry measures only the first of these, which is why a woman can fracture with a "normal" bone mineral density and why fracture-risk tools that incorporate clinical risk factors outperform density alone.
For the gynaecologist this is squarely a reproductive-endocrine problem, not merely a geriatric one. Oestrogen is the dominant restraint on bone resorption across a woman's life, so any state of oestrogen deficiency — physiological menopause, premature ovarian insufficiency, prolonged hypothalamic amenorrhoea, surgical or medical castration — drives accelerated bone loss. Several therapies we prescribe are themselves osteopenic: depot medroxyprogesterone acetate (DMPA), gonadotrophin-releasing hormone (GnRH) agonists used for endometriosis and fibroids, and aromatase inhibitors used after breast cancer. The clinical stakes are high: a hip fracture carries roughly 20% excess mortality in the first year and leaves up to half of survivors unable to live independently, while vertebral fractures, though often clinically silent, cause height loss, kyphosis, chronic pain, and predict further fractures. This chapter covers the pathophysiology the FCOG candidate must be able to explain, then assessment and management, with the oestrogen axis and iatrogenic bone loss given the prominence they deserve. It pairs closely with climacteric-and-menopause.
Core knowledge
Normal bone biology and remodelling
Bone is metabolically active tissue under continuous turnover. Two cell lineages do the work:
- Osteoclasts — large multinucleate cells of haematopoietic (monocyte/macrophage) origin that resorb mineralised bone.
- Osteoblasts — mesenchymal-derived cells that lay down new osteoid and mineralise it; terminally differentiated osteoblasts entombed in matrix become osteocytes, the mechanosensors of bone.
Remodelling proceeds in basic multicellular units: osteoclasts excavate a resorption pit, then osteoblasts refill it. In youth these are balanced (or formation slightly exceeds resorption while peak mass accrues). The master regulatory axis is RANK / RANKL / osteoprotegerin (OPG):
- Osteoblasts and stromal cells express RANKL (receptor activator of nuclear factor-κB ligand), which binds RANK on osteoclast precursors to drive their differentiation, activation, and survival.
- OPG is a soluble decoy receptor, also made by osteoblasts, that binds RANKL and prevents it engaging RANK — it brakes resorption.
- The RANKL:OPG ratio therefore sets the tempo of bone resorption. This axis is the direct pharmacological target of denosumab (a monoclonal anti-RANKL antibody).
Why oestrogen matters
Oestrogen is profoundly bone-protective and acts at several points:
- It promotes osteoclast apoptosis and shortens osteoclast lifespan.
- It suppresses RANKL and increases OPG, lowering the RANKL:OPG ratio.
- It dampens pro-resorptive cytokines (IL-1, IL-6, TNF-α) released as oestrogen falls.
- It supports osteoblast and osteocyte survival.
When oestrogen is withdrawn — most commonly at menopause — the remodelling rate rises and resorption outpaces formation. Because each remodelling cycle transiently removes bone before it is replaced, an increased number of active units means a larger transient deficit; more importantly, the deeper resorption pits perforate and disconnect trabecular plates, an architectural loss that cannot be fully restored by simply adding mineral back. This is the mechanism behind the rapid bone loss of the early postmenopausal years.
Figure B1.1 — Oestrogen withdrawal raises RANKL, lowers OPG, releases cytokine signalling, and shifts remodelling toward osteoclast-driven trabecular loss.
Peak bone mass and the trajectory of loss
Bone mass rises through childhood and adolescence, with the great majority accrued by the late teens and peak bone mass reached by the late twenties. Peak bone mass is 60–80% genetically determined, with nutrition (calcium, protein, vitamin D), physical activity, body weight, and sex steroid sufficiency during adolescence as the major modifiable contributors. This is precisely why DMPA use in adolescents, or hypothalamic amenorrhoea from the female athlete triad / relative energy deficiency in sport, matters: they blunt accrual at the very window when peak mass is being laid down.
After the peak, bone is slowly lost with age in both sexes. In women a phase of accelerated loss is superimposed for roughly the first 5–10 years after menopause — up to ~2% per year from trabecular sites — driven by oestrogen withdrawal, before settling to a slower age-related rate.
- Trabecular bone (vertebral bodies, distal radius, proximal femur) has a large surface area, high turnover, and is lost first and fastest after menopause — hence early vertebral and Colles' (distal radius) fractures.
- Cortical bone (shafts of long bones, predominates at the hip) is lost more gradually with ageing — hence hip fractures dominate later in life.
Figure B1.2 — Bone mass trajectory showing the peak-mass window, accelerated early postmenopausal trabecular loss, and the fracture pattern over time.
Classification
- Primary osteoporosis
- Type I (postmenopausal) — predominantly oestrogen-deficiency–driven, trabecular, presenting with vertebral crush and distal radius fractures in the years after menopause.
- Type II (senile/age-related) — affects cortical and trabecular bone in both sexes with advancing age; classic fracture is the hip.
- Secondary osteoporosis — bone loss attributable to an identifiable disease or drug. Always considered, and especially likely in premenopausal women, in men, and when the Z-score is low. Important causes:
- Endocrine — hypogonadism (including premature ovarian insufficiency, hypothalamic amenorrhoea, hyperprolactinaemia), thyrotoxicosis, primary hyperparathyroidism, Cushing's syndrome, poorly controlled diabetes.
- Drugs — glucocorticoids (the commonest secondary cause), DMPA, GnRH agonists, aromatase inhibitors, prolonged heparin, some anticonvulsants, proton-pump inhibitors, SSRIs, thiazolidinediones.
- Gastrointestinal — coeliac disease, inflammatory bowel disease, malabsorption, post-bariatric surgery, chronic liver disease.
- Other — chronic kidney disease–mineral bone disorder, multiple myeloma, rheumatoid arthritis, anorexia nervosa, immobilisation.
Defining osteoporosis by bone densitometry — the WHO categories
Dual-energy X-ray absorptiometry (DXA) reports a T-score (standard deviations from the young adult reference mean) and a Z-score (SD from an age- and sex-matched mean). The WHO densitometric categories, derived for postmenopausal women, are:
| Category | T-score |
|---|---|
| Normal | ≥ −1.0 |
| Osteopenia (low bone mass) | −1.0 to −2.5 |
| Osteoporosis | ≤ −2.5 |
| Severe / established osteoporosis | ≤ −2.5 plus a fragility fracture |
Use the T-score in postmenopausal women and men ≥50. Use the Z-score in premenopausal women, men <50, and children — a Z-score ≤ −2.0 is "below the expected range for age" and should prompt a search for secondary causes. Crucially, osteoporosis can also be diagnosed clinically — irrespective of T-score — when a fragility fracture (a fracture from a fall at standing height or less, or spontaneously) occurs at the hip or spine.
Assessment
History
- Fracture history — any low-trauma fracture as an adult (a fragility fracture is itself diagnostic and the strongest predictor of the next one); height loss, back pain suggesting vertebral fracture.
- Reproductive/menopausal history — age at menarche and menopause, episodes of prolonged amenorrhoea, premature ovarian insufficiency, surgical menopause, lactational and parity history.
- Drug history — glucocorticoids (dose, duration), DMPA, GnRH agonists (with or without add-back), aromatase inhibitors, anticonvulsants, PPIs, heparin.
- Secondary-cause screen — symptoms of thyrotoxicosis, malabsorption/coeliac, hyperparathyroidism, Cushing's; chronic inflammatory or renal disease.
- Lifestyle and falls — smoking, alcohol (≥3 units/day), physical inactivity, low dietary calcium, low body weight, falls and frailty.
- Family history — parental hip fracture (a FRAX input).
Examination
- Height (and documented height loss >4 cm suggesting vertebral fracture), thoracic kyphosis, BMI (low BMI is a risk factor).
- Signs of a secondary cause (thyroid, Cushingoid features, signs of hypogonadism).
- Gait, balance, and falls-risk assessment.
Investigations
- DXA of the lumbar spine (L1–L4) and proximal femur (femoral neck and total hip) — the standard for diagnosis and monitoring. Degenerative spinal change and aortic calcification falsely raise lumbar readings in older women, so the hip is often more reliable then.
- FRAX® — the WHO fracture-risk algorithm giving the 10-year probability of a major osteoporotic fracture and of hip fracture from clinical risk factors (age, sex, BMI, prior fracture, parental hip fracture, smoking, glucocorticoids, rheumatoid arthritis, secondary osteoporosis, alcohol), with or without femoral-neck BMD. A validated South African FRAX model exists, which is particularly valuable where DXA access is limited — the strategy is to risk-stratify with FRAX and reserve/target DXA and treatment accordingly.
- Lateral spine imaging / vertebral fracture assessment (VFA) — to detect the silent vertebral fractures that change management.
- Bloods to exclude secondary causes — FBC and ESR, serum calcium, phosphate, alkaline phosphatase, creatinine/eGFR, liver enzymes, TSH, 25-hydroxyvitamin D, PTH if calcium abnormal, coeliac serology, serum/urine protein electrophoresis where myeloma is possible, and a morning testosterone in men. Correct vitamin D deficiency before starting an antiresorptive to avoid precipitating hypocalcaemia.
- Bone turnover markers (serum CTX for resorption, P1NP for formation) — not for diagnosis, but useful for monitoring response and adherence.
Management
The aim is to prevent the first fracture and any subsequent fracture, by maximising bone mass, minimising loss, and reducing falls.
Non-pharmacological foundation (everyone)
- Calcium — aim for a total intake of ~1000–1200 mg/day, diet first, supplementing only the shortfall.
- Vitamin D — 800–1000 IU/day to maintain replete 25-OH-D; correct deficiency before antiresorptives.
- Weight-bearing and resistance exercise, smoking cessation, alcohol moderation.
- Falls prevention — strength and balance training, vision and medication review, home-hazard reduction; hip protectors in selected frail patients.
Pharmacological therapy
- Bisphosphonates — first-line. Alendronate 70 mg weekly or risedronate 35 mg weekly (oral), or zoledronic acid 5 mg IV yearly. They bind hydroxyapatite and impair osteoclast function. Oral dosing requires taking the tablet fasting with water and remaining upright (oesophagitis risk); avoid if eGFR <35 mL/min. Rare but important harms: osteonecrosis of the jaw and atypical femoral fractures with long-term use — hence a "drug holiday" is considered after ~5 years of oral (or 3 years of IV) therapy in those at low-to-moderate residual risk.
- Denosumab — 60 mg subcutaneously every 6 months; a RANKL inhibitor, useful in renal impairment and high-risk patients. Critical pitfall: it must not simply be stopped — discontinuation causes a rebound rise in turnover and a risk of multiple vertebral fractures, so a follow-on antiresorptive (typically a bisphosphonate) is required if it is withdrawn.
- Menopausal hormone therapy (HRT) — prevents bone loss and reduces vertebral and hip fractures. It is first-line for prevention in women under 60 or within 10 years of menopause, particularly when they also have vasomotor symptoms, and it is the treatment of choice for bone protection in premature ovarian insufficiency (continued at least to the average age of menopause, ~51). It is not used as a first-line agent solely for osteoporosis in older women. See climacteric-and-menopause.
- Selective oestrogen receptor modulators (raloxifene) — reduce vertebral fractures and breast-cancer risk but not hip fractures, and increase venous thromboembolism risk; useful in younger postmenopausal women with predominantly spinal disease.
- Anabolic agents — teriparatide (recombinant PTH analogue) builds bone and is reserved for severe osteoporosis with multiple vertebral fractures, limited to 24 months; romosozumab (anti-sclerostin) is anabolic with antiresorptive effect, used with cardiovascular caution.
- Tibolone — a synthetic steroid with oestrogenic, progestogenic and androgenic actions; improves BMD and vasomotor symptoms in older postmenopausal women.
Managing iatrogenic and oestrogen-deficiency bone loss (the gynaecology core)
- DMPA — suppresses ovarian oestradiol and causes a reversible reduction in BMD; counsel users, encourage calcium/vitamin D and weight-bearing exercise, and review long-term use — but DMPA is not contraindicated and recovery follows discontinuation (see contraceptive-modalities).
- GnRH agonists (endometriosis, fibroids) — limit to 6 months without add-back therapy (low-dose oestrogen/progestogen or tibolone), which preserves bone while retaining symptom control.
- Aromatase inhibitors after breast cancer — anticipate bone loss; baseline DXA, bone-protective measures, and antiresorptive cover for high-risk patients.
- Glucocorticoids — institute bone protection early in anyone on prolonged or high-dose steroids; do not wait for a DXA in high-risk regimens.
- Premature ovarian insufficiency / early menopause — replace oestrogen at least until the natural age of menopause for bone and cardiovascular protection.
Figure B1.3 — Osteoporosis assessment-to-treatment pathway linking risk history, DXA/FRAX/VFA and secondary-cause screening to bone-protective treatment choices and pitfalls.
Monitoring
Repeat DXA at intervals of roughly 2–3 years (sooner for high-risk or steroid-treated patients); use bone turnover markers to confirm response and adherence; reassess fracture risk at the end of a bisphosphonate drug holiday.
Red flags / pitfalls
- Treating bone density and ignoring secondary causes — always screen, and especially when the patient is premenopausal, male, or has a low Z-score.
- Stopping denosumab without a bridging antiresorptive — precipitates rebound vertebral fractures.
- Failing to correct vitamin D deficiency before a potent antiresorptive — risk of symptomatic hypocalcaemia.
- Leaving premature ovarian insufficiency or early menopause unreplaced — accelerated bone loss and cardiovascular risk.
- GnRH agonist beyond 6 months without add-back — avoidable bone loss.
- Not looking for vertebral fractures — they are often silent yet diagnostic of osteoporosis and change treatment thresholds.
- Withholding bone protection in long-term/high-dose glucocorticoids while waiting for a scan.
- Over-reliance on a normal T-score — a fragility fracture is osteoporosis regardless of density; fracture risk also depends on bone quality and falls.
- Forgetting the adolescent peak-bone-mass window — DMPA, hypothalamic amenorrhoea, and eating disorders all blunt accrual when it matters most.
Evidence anchors
- NOFSA — National Osteoporosis Foundation of South Africa, Guideline for the Diagnosis and Management of Osteoporosis — the South African source of truth; uses the WHO BMD definition and the FRAX® South African model.
- WHO bone mineral density diagnostic categories (T-score thresholds; DXA of hip and spine).
- FRAX® — WHO Fracture Risk Assessment Tool (10-year major osteoporotic and hip fracture probability; validated South African country model).
- NOGG — National Osteoporosis Guideline Group (UK) — FRAX-based intervention thresholds (international cross-reference).
- IOF — International Osteoporosis Foundation — calcium/vitamin D and fracture-liaison-service position statements.
- NICE NG23 — Menopause: diagnosis and management — HRT for bone protection, including premature ovarian insufficiency.
- South African EML / NDoH Standard Treatment Guidelines — availability of calcium, vitamin D, alendronate, zoledronic acid.