27th February 2025

Secondary osteoporosis

Disease causes of secondary osteoporosis may be divided into those which impair bone formation and those which enhance bone resorption:

• Impaired formation: 
  • Reduced intake or malabsorption of micronutrients essential for bone development (e.g. anorexia nervosa, chronic malnutrition, gastric bypass surgery, coeliac disease, IBD, pancreatic insufficiency, chronic liver disease)
  • Deficiency of normal endocrine-mediated promotion of osteoblast activity (hypothyroidism, growth hormone deficiency, hypogonadism)
• Enhanced resorption:
  • Abnormal endocrine-mediated promotion of osteoclast activity (hyperthyroidism, primary hyperparathyroidism, diabetes mellitus, acromegaly)
  • Cytokine-mediated enhanced osteoclastogenesis in inflammatory disease states (IBD, MGUS, multiple myeloma, RA, SLE, ankylosing spondylitis, MS)
  • Renal osteodystrophy (see ‘CKD-MBD and other bone diseases’) and acid-mediated calcium removal from bone (end-stage renal disease, renal tubular acidosis)

Osteoporosis secondary to medication

For many of these diseases, the association with osteoporosis is partially explained by the frequent use of glucocorticoids, which constitute the most common cause of secondary osteoporosis through downregulation of both osteoblast numbers and activity. National guidelines, therefore, advise prescribing bone protection without assessing bone density in patients on long-term glucocorticoids if they have ever had a fragility fracture if they are female and over 70 years of age, or if they are a postmenopausal woman or man over 50 years who either has a FRAX score exceeding the intervention threshold or their glucocorticoid prescription is high-dose (the equivalent of ≥7.5mg prednisolone over 3 months).

Similarly, many instances of hypogonadism may be drug-induced, as seen in patients taking aromatase inhibitors (e.g. anastrozole, letrozole) for oestrogen-receptor positive breast cancer, GnRH agonists (e.g. goserelin, leuprorelin acetate) for prostate cancer or endometriosis, and medroxyprogesterone acetate (Depo-ProveraⓇ) as a contraceptive or as a treatment in certain cancers and gynaecological conditions.

Guidelines, therefore, suggest that men starting androgen-depriving therapies and women starting aromatase inhibitors receive a FRAX assessment. They additionally recommend that patients with a score near the intervention threshold or with additional risk factors (e.g. requiring glucocorticoids) undergo reassessment of their FRAX with BMD measurement 12-18 months (if male) or 12-24 months (if female) after initiation of treatment.

Other drug causes include PPIs, loop diuretics, SSRIs, antiepileptics (particularly enzyme-inducing drugs), heparin, thiazolidinediones, calcineurin inhibitors, and antiretrovirals.