Premenopausal Osteoporosis

Premenopausal osteoporosis is low bone mass with fragility fracture in women before the menopause. Because fractures are uncommon, a low bone density alone does not define osteoporosis in this group.

A diagnosis requires a low trauma fracture (vertebral, hip or other) with or without a low bone density (Z-score of -2.0 or lower). Many women have a secondary cause, and some have pregnancy and lactation associated osteoporosis or a heritable bone disease.

Secondary causes include glucocorticoids, anorexia nervosa and functional hypothalamic amenorrhoea, premature ovarian insufficiency, coeliac disease, hyperparathyroidism, hyperthyroidism, Cushing syndrome, chronic kidney disease, anticonvulsants, medroxyprogesterone acetate, aromatase inhibitors, inflammatory disease and heritable disorders (osteogenesis imperfecta, Ehlers-Danlos syndrome).

Pathophysiology.

Failure to reach peak bone mass or increased bone loss from oestrogen deficiency, glucocorticoids and other secondary factors lead to low bone mass. Idiopathic cases show low bone formation and architecture changes.

In pregnancy and lactation, high calcium demand and reduced bone formation can cause vertebral fractures in late pregnancy or early postpartum.

• Back pain from vertebral fractures (often in the third trimester or postpartum), peripheral fractures after low trauma, and height loss.
• Features of the secondary cause: amenorrhoea, low weight, eating disorder, diarrhoea or weight loss (coeliac disease), Cushingoid features, hot flushes.
• Family history of fractures or blue sclerae, hypermobility and dental problems.

Red flags.

• Multiple vertebral fractures or pregnancy related back pain.
• Weight loss, bone pain or raised calcium (malignancy, myeloma).

• DXA with Z-scores (not T-scores) at spine and hip. Lateral spine imaging for vertebral fractures.
• Secondary cause screen: calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin D, creatinine, alkaline phosphatase, full blood count, ESR, thyroid stimulating hormone, coeliac serology, FSH, oestradiol and prolactin, 24-hour urinary free cortisol or dexamethasone suppression if indicated, serum protein electrophoresis and 24-hour urinary calcium.
• Genetic testing (COL1A1, COL1A2 and other genes) with a family history, blue sclerae or multiple fractures. Bone biopsy is rarely needed.

Differential diagnosis.

• Osteogenesis imperfecta and other heritable bone disorders.
• Osteomalacia, myeloma and metastases.
• Pregnancy and lactation associated osteoporosis.

• Treat the secondary cause (restore weight and menses, replace oestrogen in premature ovarian insufficiency, treat coeliac disease and hyperparathyroidism, reduce glucocorticoids).
• Calcium 1000 mg daily from diet and supplements, vitamin D 800 to 2000 units daily to keep 25-hydroxyvitamin D over 50 nmol/L (20 ng/mL), weight bearing exercise, stop smoking and limit alcohol.
• Drug treatment only for fragility fracture with ongoing risk: bisphosphonates are used with caution because they remain in bone and may affect a foetus (effective contraception and counselling are needed); denosumab is avoided in women who may conceive. Teriparatide 20 micrograms subcutaneously daily for up to 24 months for severe disease or vertebral fractures.
• Pregnancy and lactation associated osteoporosis: stop breastfeeding, give calcium and vitamin D, avoid weight bearing for a short period, and consider teriparatide in severe cases (vertebral fractures usually stabilise).
• Women planning pregnancy should have their bone health reviewed beforehand.

Special groups. Adolescents and young women with eating disorders: nutritional rehabilitation and specialist team care.

Monitoring. DXA every 1 to 2 years while treated, back pain review, and calcium and vitamin D yearly.

Referral and escalation. Endocrinology or metabolic bone service for all premenopausal women with fractures.