Endocrinology::Bone Medicine (Complete)

• Basics: What Is Metabolic Bone Disease? | Bone Biology and Remodelling | Calcium, Phosphate and Vitamin D | Reading the Bone Bloods | Imaging and DXA
• Osteoporosis: Osteoporosis | Fragility Fractures | Risk Assessment: NICE NG259 and FRAX | Secondary Causes and Investigations | Lifestyle, Falls, Calcium and Vitamin D | Choosing Treatment | Bisphosphonates | Denosumab | Anabolic Treatment | HRT and Raloxifene | Treatment Duration and Drug Holidays | ONJ and Atypical Femoral Fracture | Glucocorticoid-induced Osteoporosis | Osteoporosis in Men | Hip Fracture
• Calcium disorders: Hypercalcaemia | Hypercalcaemia: Emergency Treatment | Primary Hyperparathyroidism | Familial Hypocalciuric Hypercalcaemia | Hypercalcaemia of Malignancy | Hypocalcaemia | Hypoparathyroidism | Pseudohypoparathyroidism
• Mineralisation and phosphate: Vitamin D Deficiency | Osteomalacia | Rickets | Phosphate-wasting Disorders | Phosphate, Magnesium and Refeeding
• Other bone diseases: Paget's Disease of Bone | CKD–Mineral Bone Disorder | Bone Metastases and Myeloma | Osteogenesis Imperfecta | Fibrous Dysplasia | Hypophosphatasia | Osteopetrosis | Avascular Necrosis
• Special situations: Pregnancy and Lactation | Older Adults and Frailty
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🦴 Metabolic bone disease covers conditions in which bone is too thin (osteoporosis), poorly mineralised (osteomalacia), remodelled chaotically (Paget's disease), or affected by disorders of calcium, phosphate, vitamin D and parathyroid hormone. Osteoporosis alone causes over half a million fragility fractures a year in the UK. A hip fracture kills about 1 in 4 within a year.
Your four questions for every patient: Is the bone too thin, poorly mineralised or abnormally remodelled? What do calcium, phosphate, ALP, PTH and vitamin D show? Is there an emergency (severe hyper- or hypocalcaemia)? What is the fracture risk, and how can it be reduced?

What Is Metabolic Bone Disease?

Bone is living tissue. It is constantly broken down and rebuilt, and it acts as the body's store of calcium and phosphate. Metabolic bone disease arises when:

• Too little bone: Normal bone, but not enough of it, so it fractures easily. This is osteoporosis.
• Poorly mineralised bone: The protein framework is laid down but not hardened with mineral, so the bone is soft. This is osteomalacia in adults and rickets in children, usually from vitamin D or phosphate deficiency.
• Disorganised bone: Overactive, chaotic remodelling produces large, weak, deformed bone. This is Paget's disease.
• Mineral and hormone disorders: Hyper- and hypocalcaemia, parathyroid disease and phosphate disorders, which affect bone, kidneys, nerves and heart.
• Bone involved by other disease: Kidney disease, cancer, genetic conditions.

💡 Clinical Pearl: Osteoporosis is silent until a bone breaks, and causes no pain or abnormal blood tests on its own. Bone pain with abnormal bloods (high ALP, low phosphate, abnormal calcium) suggests a different diagnosis - osteomalacia, Paget's, hyperparathyroidism or malignancy.

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Bone Biology and Remodelling

The cells:

• Osteoclasts: Large cells that resorb (dissolve) bone.
• Osteoblasts: Cells that build new bone. They lay down collagen (osteoid), which then mineralises with calcium phosphate (hydroxyapatite). Osteoblasts release alkaline phosphatase (ALP), so a raised ALP signals increased bone formation.
• Osteocytes: Osteoblasts buried in bone. They sense mechanical load and release FGF23 and sclerostin, which regulate phosphate and bone formation.

Remodelling: Osteoclasts dig a small cavity and osteoblasts fill it. In young adults the two are balanced. After about 35–40 years, and especially after the menopause (loss of oestrogen), resorption exceeds formation, and bone is lost.

The RANKL pathway: Osteoblasts produce RANKL, which activates osteoclasts, and osteoprotegerin, which blocks it. Oestrogen deficiency and glucocorticoids shift the balance towards RANKL. Denosumab works by blocking RANKL.

Peak bone mass: Reached in the late 20s and determined by genetics, nutrition, exercise and sex hormones. A low peak mass (e.g. from anorexia or delayed puberty) raises the lifetime risk of osteoporosis.

Bone types:

• Trabecular (spongy) bone in vertebrae and the ends of long bones turns over fastest. This is why vertebral fractures are often the first sign of osteoporosis and of glucocorticoid damage.
• Cortical bone forms the shafts of long bones.

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Calcium, Phosphate and Vitamin D

Three hormones keep blood calcium within a tight range:

• Parathyroid hormone (PTH): Released when calcium falls. It:
  • Releases calcium from bone.
  • Increases calcium reabsorption and phosphate excretion in the kidney.
  • Stimulates the kidney to activate vitamin D.
• Vitamin D:
  • Made in the skin by sunlight (UVB) or taken in the diet.
  • Hydroxylated in the liver to 25-hydroxyvitamin D - the storage form, which is what we measure.
  • Then hydroxylated in the kidney to 1,25-dihydroxyvitamin D (calcitriol) - the active hormone. It increases gut absorption of calcium and phosphate.
• FGF23: Made by osteocytes when phosphate is high. It makes the kidney excrete phosphate and suppresses calcitriol. Excess FGF23 causes phosphate-wasting rickets and osteomalacia.
• Calcitonin (from thyroid C cells) has a minor role in humans.

Measuring calcium: About 45% of blood calcium is bound to albumin. Use the albumin-adjusted (corrected) calcium, typically 2.20–2.60 mmol/L. In acid–base disturbance or very abnormal albumin, measure ionised calcium on a blood gas.

Magnesium matters: Magnesium is needed both to release PTH and for tissues to respond to it. Low magnesium therefore causes hypocalcaemia that will not correct until magnesium is replaced.

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Reading the Bone Bloods

The pattern of calcium, phosphate, ALP and PTH points to the diagnosis:

💡 Clinical Pearl: A raised ALP may come from bone or liver. A raised GGT suggests liver; a normal GGT suggests bone. Bone-specific ALP or ALP isoenzymes can confirm the source.

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Imaging and DXA

• DXA scan (dual-energy X-ray absorptiometry): Measures bone mineral density at the lumbar spine and hip. Results are reported as:
  • T-score: Standard deviations from a young healthy adult.
    • Normal: −1.0 or above.
    • Osteopenia: between −1.0 and −2.5.
    • Osteoporosis: −2.5 or below.
    • Severe (established) osteoporosis: −2.5 or below plus a fragility fracture.
  • Z-score: Compared with people of the same age. Used in premenopausal women, men under 50 and children. A Z-score below −2.0 means "below the expected range for age" - look for secondary causes.
• DXA pitfalls: Spinal osteoarthritis, vertebral fractures and aortic calcification falsely raise spine density. The hip is often more reliable in older people.
• Vertebral fracture assessment (VFA): A lateral spine image taken with DXA to find silent vertebral fractures. NICE NG259 suggests considering it for women aged 60 or over and men aged 70 or over.
• Plain X-rays: Show fractures, Looser's zones (osteomalacia), Paget's changes, lytic or sclerotic metastases. They cannot measure bone density.
• Isotope bone scan: Shows areas of high turnover - metastases, Paget's extent, stress fractures. Typically negative in myeloma, which is purely lytic.
• MRI: Occult fractures (e.g. hip), avascular necrosis, Charcot foot, spinal cord compression.
• Parathyroid localisation (ultrasound, sestamibi scan, 4D CT, choline PET): Only once a decision to operate has been made - never to make the diagnosis.

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Osteoporosis

Mechanism: A systemic skeletal disease of low bone mass and deterioration of bone architecture, leading to fragile bones and fractures. The bone that is present is normal in composition - there is simply too little of it.

How common: About 1 in 2 women and 1 in 5 men over 50 will have a fragility fracture.

Risk factors:

• Age and female sex; early menopause or premature ovarian insufficiency.
• Previous fragility fracture - the strongest predictor of another.
• Glucocorticoid use.
• Low BMI (below 18.5–19).
• Parental hip fracture.
• Smoking; alcohol over about 14 units a week.
• Falls.
• Immobility.
• Rheumatoid arthritis and other inflammatory diseases.
• Many secondary causes (see Secondary Causes).

Clinical pattern:

• No symptoms until fracture.
• Vertebral fractures: Often silent, or cause sudden back pain, height loss (more than 4 cm), kyphosis ("dowager's hump"), breathlessness and abdominal crowding.
• Wrist (Colles') fracture: Often the first fracture, in women in their 50s–60s.
• Hip fracture: In older people, often after a fall.

Blood tests are normal, but are needed to exclude secondary causes and other bone diseases.

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Fragility Fractures

Definition: A fracture from a fall from standing height or less, or with no trauma at all, that would not break a healthy bone.

Typical sites:

• Vertebrae.
• Hip (proximal femur).
• Wrist (distal radius).
• Proximal humerus.
• Pelvis.
• Ribs.

Fingers, toes, face and skull are not typical osteoporotic sites.

The fracture cascade: One fragility fracture roughly doubles the risk of another. The risk is highest in the first 1–2 years - the "imminent fracture risk". Every fragility fracture is therefore a chance to prevent the next one.

Fracture Liaison Services (FLS): Systematically identify people aged 50 and over with a fragility fracture, assess their bone health and falls risk, and start treatment. They are highly cost-effective, but are not yet available everywhere.

💡 Clinical Pearl: A vertebral fracture seen on any chest X-ray or CT is a fragility fracture, even if the patient has no symptoms. Report it, act on it, and check for myeloma if it is unexplained.

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Risk Assessment: NICE NG259 and FRAX

NICE published NG259: Osteoporosis - Risk Assessment in July 2026, updating its 2012 guidance. Treatment recommendations are due in a further update (expected 2027). Until then, UK treatment decisions follow NOGG 2022 (National Osteoporosis Guideline Group).

Who to assess (NICE NG259):

• Assess adults aged 50 or over, and postmenopausal women, who have:
  • A previous fragility fracture, or
  • Current or frequent systemic glucocorticoid use (e.g. prednisolone 5 mg or more daily for over 3 months, or frequent higher-dose courses) - unless it is replacement therapy for adrenal insufficiency.
• Consider assessing:
  • Women aged 65 or over and men aged 75 or over.
  • People aged 50–74 (or postmenopausal women under 65) with risk factors: two or more falls in the past year, a parent or sibling with hip fracture, BMI below 18.5, current smoking, alcohol over 14 units a week, and others.
• Under 50 and premenopausal:
  • Assess if there is a previous hip or vertebral fragility fracture, or two or more major osteoporotic fractures.
  • Consider if there are other major risk factors - e.g. another fragility fracture, glucocorticoids, untreated early menopause or premature ovarian insufficiency.
• Trans and non-binary people: Individualised assessment, considering sex registered at birth, hormonal history and current hormone treatment.

Risk tools: FRAX (which can include femoral neck BMD) and QFracture estimate the 10-year probability of a major osteoporotic fracture and of a hip fracture.

DXA (NICE NG259):

• Offer DXA to people aged 30 or over with a previous hip or vertebral fragility fracture, a major osteoporotic fracture in the last 2 years, or two or more fragility fractures. A risk calculation is not needed first.
• Consider DXA when the 10-year major osteoporotic fracture risk is 10% or more, to guide treatment decisions.
• Baseline DXA before treatment: Usually done, unless not tolerated, not feasible or not needed.
• If DXA would be significantly delayed: Fast-track people likely to need anabolic treatment (scan within 6 weeks), and start antiresorptive treatment in those unlikely to need anabolic treatment.
• Repeat DXA: Usually not needed within 2 years.

NOGG treatment thresholds:

• NOGG uses FRAX probabilities plotted against age-dependent intervention thresholds, sorting people into low, high and very high risk.
• Postmenopausal women and men over 50 with a previous fragility fracture can be considered for treatment without DXA if needed - especially vertebral fractures in older people.

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Secondary Causes and Investigations

Look for a secondary cause in everyone with osteoporosis - especially men, premenopausal women, a low Z-score or unusual fractures. Treating the cause improves bone.

Secondary causes:

• Endocrine:
  • Hypogonadism - early menopause, male hypogonadism, androgen deprivation therapy for prostate cancer, aromatase inhibitors for breast cancer.
  • Hyperthyroidism or over-replacement with levothyroxine.
  • Primary hyperparathyroidism.
  • Cushing's syndrome.
  • Type 1 and type 2 diabetes.
  • Anorexia nervosa.
• Gastrointestinal: Coeliac disease, inflammatory bowel disease, chronic liver disease, bariatric surgery, malabsorption.
• Inflammatory: Rheumatoid arthritis, ankylosing spondylitis, SLE.
• Haematological: Myeloma, MGUS, systemic mastocytosis, thalassaemia.
• Drugs:
  • Glucocorticoids.
  • Aromatase inhibitors and androgen deprivation.
  • Enzyme-inducing anticonvulsants.
  • PPIs (modest).
  • Thiazolidinediones.
  • Long-term heparin.
  • Medroxyprogesterone (depot).
  • Excess levothyroxine.
• Other: CKD, COPD, HIV, immobility, alcohol excess, smoking.

Baseline investigations:

• FBC, ESR/CRP.
• U&E and eGFR (drug choice).
• Bone profile: Calcium, phosphate, ALP, albumin.
• LFTs.
• TFTs.
• 25-OH vitamin D.
• PTH if calcium is abnormal.
• Serum protein electrophoresis and free light chains (myeloma), especially with vertebral fractures.
• Coeliac serology (anti-TTG).
• Men: Testosterone, SHBG, LH and FSH.
• Tests for Cushing's, mastocytosis and others when clinically suggested.

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Lifestyle, Falls, Calcium and Vitamin D

• Exercise: Weight-bearing and muscle-strengthening exercise, plus balance training (e.g. FaME or Otago programmes, tai chi) to prevent falls.
• Falls prevention - most hip fractures follow a fall:
  • Review drugs: sedatives, antihypertensives causing postural hypotension, anticholinergics.
  • Check vision and treat cataracts.
  • Home hazard assessment.
  • Footwear.
  • Continence.
• Stop smoking; limit alcohol to 14 units a week or less.
• Calcium: Aim for 700–1,200 mg a day, preferably from the diet (dairy, fortified foods, leafy greens). Use the online calcium calculator from the Royal Osteoporosis Society. Supplement only when the diet is inadequate.
• Vitamin D: 800–1,000 units daily for people with or at risk of osteoporosis, and for housebound or care-home residents. Check and replace vitamin D before starting IV bisphosphonates or denosumab, to avoid hypocalcaemia.
• Hip protectors: May help in care homes, if worn.
• Protein and nutrition: Adequate intake, especially in frail older people.

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Choosing Treatment

Bone drugs work in one of two ways:

• Antiresorptive: Slow osteoclasts down to reduce bone loss - bisphosphonates, denosumab, HRT, raloxifene.
• Anabolic: Stimulate osteoblasts to build new bone - teriparatide, abaloparatide, romosozumab. These produce bigger, faster gains.

NOGG 2022 approach:

• High risk: Oral bisphosphonate (alendronic acid or risedronate) first-line. If not tolerated, unsuitable or ineffective: IV zoledronic acid or denosumab. HRT is an option in younger postmenopausal women.
• Very high risk - consider anabolic treatment first, followed by an antiresorptive. Features include:
  • A recent vertebral fracture (within 2 years).
  • Two or more vertebral fractures.
  • A T-score of −3.5 or lower.
  • High-dose glucocorticoids (prednisolone 7.5 mg or more daily for 3 months or more).
  • A FRAX probability well above the intervention threshold.
• Sequence matters: An anabolic drug followed by an antiresorptive gives the best gains. Starting an antiresorptive first blunts a later anabolic response. An anabolic course must always be followed by an antiresorptive, or the gains are lost.
• Kidney function:
  • Avoid oral bisphosphonates if creatinine clearance is below about 35 mL/min, and zoledronic acid if below 35 mL/min.
  • Denosumab can be used in CKD but carries a higher hypocalcaemia risk.
  • Exclude CKD–mineral bone disorder in advanced CKD.

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Bisphosphonates

How they work: They bind to bone mineral and are taken up by osteoclasts, which they inactivate. They stay in the skeleton for years, which is why "drug holidays" are possible.

• Alendronic acid 70 mg once weekly (or risedronate 35 mg once weekly):
  • Reduces vertebral fractures by about 40–70%, and hip and other fractures by about 20–40%.
  • How to take it (poorly absorbed, and can damage the oesophagus):
    • On an empty stomach, first thing in the morning.
    • With a full glass of plain water.
    • Stay upright for 30 minutes before eating, drinking anything else or taking other medicines.
    • Separate from calcium supplements.
  • Avoid with oesophageal stricture or achalasia, inability to stay upright, or creatinine clearance below about 35 mL/min.
• Ibandronic acid: Monthly oral or 3-monthly IV - reduces vertebral fractures.
• Zoledronic acid 5 mg IV once a year:
  • Reduces vertebral, hip and other fractures.
  • Useful when oral drugs are unsuitable, not tolerated or not absorbed.
  • After a hip fracture, it reduces further fractures and mortality.
  • Before giving: Check calcium and vitamin D (and correct deficiency), renal function and hydration.
  • Avoid if creatinine clearance is below 35 mL/min.
  • Give over at least 15 minutes.
• Side effects:
  • Upper GI irritation and oesophagitis (oral).
  • Acute phase reaction after the first IV dose - flu-like symptoms for 1–3 days; give paracetamol.
  • Hypocalcaemia.
  • Musculoskeletal pain.
  • Eye inflammation (uveitis, scleritis).
  • Atrial fibrillation (IV, rare).
  • Rarely, osteonecrosis of the jaw and atypical femoral fractures.

💡 Clinical Pearl: Many "treatment failures" on alendronate are actually taking it wrongly - with breakfast, tea or calcium. Check how the patient takes it before switching.

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Denosumab

• How it works: A monoclonal antibody against RANKL, which stops osteoclast formation and activity.
• Dose: 60 mg SC every 6 months for osteoporosis (the cancer dose is different - 120 mg every 4 weeks).
• Effect: Reduces vertebral, hip and non-vertebral fractures. Bone density continues to rise over 10 years of treatment.
• Uses:
  • When bisphosphonates are unsuitable or not tolerated.
  • CKD - no renal clearance, but monitor calcium closely.
  • Men on androgen deprivation and women on aromatase inhibitors.
• Before each dose: Check calcium and vitamin D. It can cause significant hypocalcaemia, especially in CKD and vitamin D deficiency.
• Stopping denosumab - the key safety issue: When it stops, bone turnover rebounds above baseline. Bone density falls rapidly, and multiple vertebral fractures can occur within months (MHRA warning).
  • Never stop it or delay a dose without a plan. Doses must be given on time (within 4 weeks of the due date).
  • If stopping, give a bisphosphonate - usually zoledronic acid about 6 months after the last denosumab dose - and monitor.
• Other side effects: Skin infections and eczema; rarely, osteonecrosis of the jaw and atypical femoral fractures.

⚠️ Safety Pearl: Missed or delayed denosumab injections cause "rebound" vertebral fractures. Ensure a recall system, and never stop denosumab without a plan to transition to a bisphosphonate.

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Anabolic Treatment

Anabolic drugs build new bone, producing larger and faster increases in density and greater fracture reduction than antiresorptives in very high-risk patients. They are prescribed by specialists.

• Teriparatide (a PTH fragment):
  • Dose: 20 micrograms SC daily for up to 24 months (once per lifetime).
  • How it works: Intermittent PTH stimulates osteoblasts - unlike the bone loss caused by continuously high PTH.
  • Benefit: Reduces vertebral and non-vertebral fractures; very effective in glucocorticoid-induced osteoporosis.
  • Side effects: Nausea, dizziness, leg cramps, mild hypercalcaemia.
  • Avoid with hypercalcaemia, Paget's disease, unexplained raised ALP, open growth plates, previous skeletal radiotherapy, or bone malignancy (a theoretical osteosarcoma risk).
• Abaloparatide (a PTHrP analogue):
  • Dose: 80 micrograms SC daily for up to 18 months.
  • NICE TA991 recommends it as an option for postmenopausal women at very high fracture risk in specified circumstances.
• Romosozumab (anti-sclerostin antibody):
  • Dose: 210 mg SC monthly for 12 months.
  • How it works: Blocks sclerostin, so it both stimulates formation and reduces resorption - a "dual action".
  • NICE TA791: For severe osteoporosis in postmenopausal women with a major osteoporotic fracture within 24 months who are at imminent high risk.
  • Contraindicated after previous MI or stroke (a cardiovascular signal in trials).
• After any anabolic course: Always follow with an antiresorptive (usually zoledronic acid, alendronate or denosumab) to consolidate the gains.

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HRT and Raloxifene

• Hormone replacement therapy (HRT):
  • Prevents bone loss and reduces fractures.
  • First-line for women with premature ovarian insufficiency or early menopause, at least until the average age of menopause (about 51).
  • A reasonable choice for bone protection in women under 60 with menopausal symptoms.
  • The benefit wears off after stopping.
  • Discuss risks: breast cancer (combined HRT), VTE (oral), stroke.
• Raloxifene 60 mg daily (a selective oestrogen receptor modulator):
  • Reduces vertebral fractures (not hip), and reduces breast cancer risk.
  • Side effects: Hot flushes, leg cramps, VTE and possibly fatal stroke. Avoid with previous VTE.
  • Rarely used now.
• Testosterone in hypogonadal men improves bone density, but is not a substitute for bone treatment when the fracture risk is high.

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Treatment Duration and Drug Holidays

Bisphosphonates persist in bone, and very long use increases rare side effects. Treatment is therefore reviewed rather than continued indefinitely (NOGG):

• Oral bisphosphonates: Review after 5 years. Continue for up to 10 years if the patient is still high risk:
  • Age 75 or over.
  • Previous hip or vertebral fracture.
  • A fracture during treatment.
  • Ongoing glucocorticoids.
  • A hip T-score of −2.5 or lower.
• Zoledronic acid: Review after 3 years; continue to 6 years if still high risk.
• Drug holiday: If not high risk, stop for typically 18 months to 3 years. Then reassess fracture risk (FRAX with or without DXA) and restart if risk increases or a fracture occurs.
• Denosumab: no holidays. It must be continued or transitioned to a bisphosphonate (see Denosumab).
• Anabolic courses: Fixed duration (teriparatide 24 months, abaloparatide 18 months, romosozumab 12 months), always followed by antiresorptive treatment.
• Monitoring:
  • Adherence and technique.
  • New fractures and height loss.
  • Repeat DXA usually no sooner than 2 years, unless clinically needed.
  • Bone turnover markers (e.g. P1NP, CTX) can check response and adherence in specialist services.

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ONJ and Atypical Femoral Fracture

• Medication-related osteonecrosis of the jaw (ONJ):
  • What it is: Exposed, dead jaw bone persisting for 8 weeks or more.
  • Risk: Very rare with osteoporosis doses (about 1 in 10,000 patient-years), but much higher with the high doses used in cancer.
  • Risk factors: Dental extractions, poor oral hygiene, ill-fitting dentures, smoking, glucocorticoids, diabetes and chemotherapy.
  • Prevention:
    • Advise good oral hygiene and regular dental check-ups.
    • Complete necessary dental work before starting treatment where practical - but do not delay osteoporosis treatment for routine dental care.
    • Tell the dentist about bone medicines.
• Atypical femoral fracture:
  • What it is: A rare transverse stress fracture of the femoral shaft, after low or no trauma, associated with long-term bisphosphonates and denosumab.
  • Warning signs: Thigh or groin pain for weeks or months beforehand. Fractures are often bilateral.
  • Action:
    • Ask about thigh pain at review.
    • X-ray both femurs if present.
    • Stop the drug if confirmed, and refer to orthopaedics (prophylactic fixation may be needed).
• Osteonecrosis of the external auditory canal: Rare; ear pain or discharge on antiresorptives (MHRA).
• Perspective: For high-risk patients, the number of fractures prevented far outweighs these rare harms. Explain this to patients who are worried.

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Glucocorticoid-induced Osteoporosis

Mechanism: Glucocorticoids suppress osteoblasts (reducing bone formation), increase resorption, reduce gut calcium absorption, cause muscle weakness and lower sex hormones. Bone loss is rapid in the first 3–6 months, affects trabecular bone most (vertebrae), and fractures occur at higher bone densities than in postmenopausal osteoporosis. The risk is dose-dependent, but even about 2.5–7.5 mg prednisolone daily increases fracture risk.

Management (NOGG):

• Use the lowest effective glucocorticoid dose, steroid-sparing agents, and inhaled or topical routes where possible.
• Give bone protection from the start, without waiting for DXA, in:
  • Women aged 70 or over.
  • People with a previous fragility fracture.
  • People taking high doses (prednisolone 7.5 mg or more daily for 3 months or more).
  For others, use FRAX (adjusted for glucocorticoid dose) with or without DXA.
• First-line: An oral bisphosphonate (alendronate or risedronate), plus adequate calcium and vitamin D.
• Alternatives: Zoledronic acid or denosumab.
• Very high risk (e.g. multiple vertebral fractures): Consider teriparatide, which is superior to alendronate in glucocorticoid-induced osteoporosis.
• Stopping steroids: Fracture risk falls after steroids stop. Review the need for bone protection, but make sure there is a plan if the patient is on denosumab.

💡 Clinical Pearl: Every patient starting long-term oral steroids needs a bone protection decision on the same day - for example a patient with giant cell arteritis or polymyalgia on high-dose prednisolone.

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Osteoporosis in Men

• Why it matters: About 1 in 5 men over 50 will have a fragility fracture. Men who break a hip have higher mortality than women.
• Secondary causes are found in up to half:
  • Hypogonadism, including androgen deprivation therapy for prostate cancer.
  • Alcohol excess.
  • Glucocorticoids.
  • Smoking.
  • Coeliac disease.
  • Myeloma.
  • Hypercalciuria.
  • Liver disease.
  • Anticonvulsants.
• Investigations: As for women, plus testosterone, SHBG, LH and FSH, PSA where relevant, and a myeloma screen.
• Treatment: Alendronate, risedronate, zoledronic acid, denosumab (licensed in men, including on androgen deprivation), or teriparatide. Testosterone replacement for hypogonadism, unless contraindicated.

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Hip Fracture

Why it matters: The most serious osteoporotic fracture - about 70,000–76,000 a year in the UK. Mortality is about 25–30% at 1 year, and many survivors lose independence.

Presentation: An older person who has fallen, with hip or groin pain and inability to bear weight. The leg may be shortened and externally rotated. X-rays can miss occult fractures - get an MRI (or CT) if suspected.

Management (NICE CG124 and the National Hip Fracture Database):

• Early analgesia, including a fascia iliaca or femoral nerve block.
• Surgery on the day of or the day after admission (within 36 hours).
• Orthogeriatric care from admission.
• Delirium prevention.
• Early mobilisation (day 1 after surgery).
• Nutrition.
• Falls and bone health assessment.

Bone protection after hip fracture: Most patients should start treatment before discharge or soon after.

• IV zoledronic acid is often preferred - no swallowing or adherence issues, and a mortality benefit.
• Give it once vitamin D is replete and the patient has recovered from surgery, commonly from about 2 weeks.
• Check renal function and calcium first.

💡 Clinical Pearl: A hip fracture is a medical emergency in a surgical setting. Its outcome depends as much on the orthogeriatrician (delirium, anaemia, fluids, bone health) as on the operation.

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Hypercalcaemia

Mechanism: Calcium enters the blood faster than the kidney and bone can clear it, from bone resorption, gut absorption or reduced renal excretion. Over 90% of cases are due to primary hyperparathyroidism (in outpatients) or malignancy (in inpatients).

The first step is to measure PTH:

• PTH high or inappropriately normal (PTH-mediated):
  • Primary hyperparathyroidism.
  • Tertiary hyperparathyroidism.
  • Familial hypocalciuric hypercalcaemia.
  • Lithium.
• PTH suppressed (non-PTH-mediated):
  • Malignancy - PTHrP, bone metastases, myeloma.
  • Vitamin D excess - over-supplementation.
  • Granulomatous disease making calcitriol - sarcoidosis, TB.
  • Lymphoma.
  • Thiazides.
  • Milk-alkali syndrome (excess calcium carbonate).
  • Thyrotoxicosis.
  • Adrenal insufficiency.
  • Immobilisation.
  • Vitamin A excess.

Clinical pattern - "bones, stones, abdominal groans and psychic moans":

• General: Thirst, polyuria (calcium causes nephrogenic diabetes insipidus), dehydration.
• Gut: Constipation, nausea, abdominal pain, pancreatitis, peptic ulcer.
• Kidney: Renal stones, nephrocalcinosis, AKI.
• Brain: Fatigue, low mood, confusion, drowsiness, coma.
• Heart: Short QT, arrhythmias.
• Bone: Pain, fractures.

Severity (albumin-adjusted calcium):

• Mild: 2.6–3.0 mmol/L - often asymptomatic.
• Moderate: 3.0–3.5 mmol/L.
• Severe: Above 3.5 mmol/L, or any level with significant symptoms - emergency.

Investigations:

• Repeat the calcium.
• PTH.
• U&E, phosphate, ALP.
• Magnesium.
• 25-OH vitamin D.
• ECG.
• If PTH is suppressed - look for malignancy:
  • Myeloma screen.
  • Chest X-ray or CT.
  • PSA, breast examination.
  • PTHrP and 1,25-dihydroxyvitamin D where needed.
  • ACE for sarcoid.
  • TFTs.

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Hypercalcaemia: Emergency Treatment

Severe or symptomatic hypercalcaemia: patients are usually very dry, because the polyuria and vomiting cause dehydration, which in turn reduces calcium excretion - a vicious cycle. Follow the Society for Endocrinology emergency guidance:

• 1. Rehydrate with IV 0.9% sodium chloride, typically 4–6 L in the first 24 hours.
  • Adjust for age, heart and kidney function.
  • Monitor fluid balance, U&E, calcium and magnesium.
  • This alone lowers calcium noticeably.
• 2. Stop contributing drugs: Thiazides, lithium, calcium and vitamin D supplements.
• 3. IV bisphosphonate once rehydrated:
  • Zoledronic acid 4 mg IV over 15 minutes, or pamidronate 30–90 mg IV.
  • Adjust or choose carefully in renal impairment.
  • Calcium falls over 2–4 days, with the maximum effect at about 1 week.
• Loop diuretics: Only to manage fluid overload after full rehydration - not as routine treatment.
• Calcitonin: Works within hours but its effect fades within 48 hours. Used as a bridge.
• Glucocorticoids (e.g. prednisolone 20–40 mg daily): For calcitriol-driven hypercalcaemia - sarcoidosis, lymphoma, vitamin D toxicity.
• Denosumab: For hypercalcaemia that does not respond to bisphosphonates, or when renal function is poor (specialist).
• Cinacalcet (calcimimetic): For parathyroid carcinoma, or for primary hyperparathyroidism when surgery is not possible.
• Haemodialysis: For life-threatening hypercalcaemia with renal failure.
• Treat the cause: Parathyroidectomy, cancer treatment, etc.

⚠️ Safety Pearl: Give fluids first, bisphosphonate second. Giving furosemide to a dehydrated hypercalcaemic patient worsens dehydration, AKI and hypercalcaemia.

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Primary Hyperparathyroidism

Mechanism: One or more parathyroid glands make too much PTH, independent of the calcium level.

• Single adenoma: About 85%.
• Multigland hyperplasia: About 10–15% - think MEN1 and MEN2A.
• Parathyroid carcinoma: Under 1% - very high calcium and PTH, and a neck mass.

It is the commonest cause of hypercalcaemia, most often in postmenopausal women. Most cases are found on routine blood tests.

Clinical pattern:

• Often asymptomatic, or with vague fatigue, low mood, thirst and constipation.
• End-organ effects:
  • Kidney stones.
  • Osteoporosis - especially at the forearm (cortical bone) - and fragility fractures.
  • Reduced eGFR.
  • Rarely pancreatitis.
  • Osteitis fibrosa cystica in severe, long-standing disease - subperiosteal erosions of the phalanges, "pepper-pot" skull, brown tumours.

Diagnosis (NICE NG132):

• Raised albumin-adjusted calcium with a PTH that is raised or inappropriately normal. A normal PTH in hypercalcaemia is abnormal - it should be suppressed.
• Check vitamin D and replace it if low.
• Exclude familial hypocalciuric hypercalcaemia with a urine calcium:creatinine clearance ratio.
• Assess end-organ damage: renal ultrasound (stones), eGFR, DXA (including the forearm).
• Consider genetic testing in people under 40, with a family history, or with multigland disease or MEN features.