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.