Secondary Causes of Osteoporosis
On this page
Direct answer
Up to half of men with osteoporosis — and most premenopausal women and younger adults presenting with fragility fracture — have a secondary cause, with glucocorticoids heading the list, followed by hypogonadism, alcohol, smoking, hyperthyroidism, hyperparathyroidism, vitamin D deficiency, malabsorption including coeliac disease, chronic kidney disease and multiple myeloma. The laboratory net is therefore cast wide at first diagnosis: full blood count and erythrocyte sedimentation rate, calcium, phosphate, alkaline phosphatase, renal and liver biochemistry, thyroid function, parathyroid hormone, 25-hydroxyvitamin D, testosterone in men, coeliac serology, serum and urine electrophoresis, and 24-hour urinary calcium. Glucocorticoid-induced osteoporosis, the single commonest secondary form, is both dose- and duration-dependent (fracture risk rises within three months of prednisolone above about 2.5-7.5 mg daily), damages bone fastest in the first year, and current guidance favours anabolic agents (teriparatide) over bisphosphonates in patients at high fracture risk.
What you must remember
- The big four to recite: glucocorticoids (drug cause number one), hypogonadism (including aromatase inhibitors, androgen deprivation, premature menopause), alcohol and tobacco; then endocrine — thyrotoxicosis, primary hyperparathyroidism, Cushing syndrome, prolactinoma, diabetes.
- GI and malabsorption: coeliac disease (screen every osteoporotic with unexplained low bone mass), bariatric surgery, inflammatory bowel disease (disease plus steroids), lactose-restricted diets and chronic PPI use reducing calcium absorption.
- Malignancy masquerade: multiple myeloma and bone metastases — the reason electrophoresis and a blood count are mandatory in any elderly patient with osteoporosis, anaemia, raised ESR or back pain out of proportion.
- Drug list worth memorising: glucocorticoids, aromatase inhibitors, androgen deprivation therapy, excessive levothyroxine (TSH-suppressive), antiepileptics (enzyme inducers lower vitamin D), PPIs, thiazolidinediones, heparin, ciclosporin, SSRIs (modest), SGLT2 inhibitors (fall-related concerns debated).
- Workup panel: FBC, ESR/CRP, calcium, phosphate, ALP, creatinine and eGFR, LFTs, TSH, PTH, 25-OH vitamin D, total testosterone (men), tissue transglutaminase IgA (with total IgA), serum protein electrophoresis with serum free light chains, and 24-hour urinary calcium to exclude hypercalciuria and calciopenic osteomalacia.
- Glucocorticoid-induced osteoporosis numbers: risk rises above about 2.5-7.5 mg prednisolone daily for 3 or more months; vertebral fractures first (trabecular bone loses fastest); reassess fracture risk at 12 months on continued steroids; calcium plus vitamin D as foundation for all.
- Treatment hierarchy in GIOP: for high-risk patients, guidelines favour teriparatide (anabolic) over oral bisphosphonates; denosumab and zoledronate are alternatives; protect while steroids run, not after the first fracture.
- Clues screaming secondary: young age, Z-score below −2 in premenopausal women or men under 50, fragility fracture despite normal BMD, unusual fracture sites, and rapid bone loss on serial DEXA — all trigger the full panel, not just vitamin D.
A fracture clinic consultation
A 58-year-old man presents after lifting a suitcase with sudden dorsal back pain; a lateral radiograph shows a wedge fracture at T8, and DEXA gives a T-score of −3.2 at the spine. He is not on steroids, but he has mild anaemia (Hb 10.6), ESR 62, and a history of loose stools. The panel runs: serum electrophoresis returns a monoclonal IgG kappa band with skewed free light chains — myeloma, explaining anaemia, ESR and fracture, and changing the entire management toward haematology; his osteoporosis treatment now must be myeloma-directed (with bisphosphonate-type antiresorption as an anchor, usually zoledronate). Contrast a 62-year-old woman on prednisolone 10 mg daily for two years with a T-score of −2.8: glucocorticoid-induced osteoporosis — she receives calcium and vitamin D, a FRAX-adjusted risk assessment, and because she is at high fracture risk with a vertebral fracture, teriparatide for the anabolic-first strategy, transitioning later to an antiresorptive to preserve gains. Had her coeliac serology been positive instead, gluten-free diet plus repletion would come before any osteoporosis drug verdict. One fracture, three different secondary diseases, three different pathways — the workup, not the DEXA, decides.
Where students slip
The reflex is to start bisphosphonates and skip the panel; the exam punishes exactly that in stems with anaemia, high ESR or young age, where the hidden answer is myeloma. The second miss is GIOP's first-year kinetics — bone loss is fastest early, so protection starts with the steroid, not after the first year. Third, candidates forget that teriparatide is contraindicated with prior skeletal radiation and is relatively avoided in myeloma-driven bone disease, a nuance vivas explore.
Frequently asked questions
Which is the commonest secondary cause of osteoporosis?
Glucocorticoid therapy — fracture risk climbs within months of prednisolone above roughly 2.5-7.5 mg daily, with vertebral (trabecular) bone lost fastest in the first year.
Which investigations screen for secondary osteoporosis?
FBC, ESR, calcium, phosphate, ALP, renal and liver function, TSH, PTH, 25-OH vitamin D, testosterone in men, coeliac serology, serum electrophoresis with free light chains, and 24-hour urinary calcium.
Why is multiple myeloma excluded in new osteoporosis?
Because myeloma masquerades as age-related osteoporosis while anaemia, raised ESR and fragility fractures accumulate — electrophoresis and free light chains change prognosis and therapy entirely.
Which anti-osteoporosis drug is preferred in glucocorticoid-induced disease at high risk?
Teriparatide, the anabolic agent favoured over oral bisphosphonates by current guidance for high-risk glucocorticoid-treated patients, followed by antiresorptive consolidation.
What Z-score threshold triggers a secondary-cause search in younger patients?
A Z-score of −2 or lower in premenopausal women, men under 50, or children, plus any fragility fracture in these groups — populations where secondary causes dominate.