Osteomalacia and vitamin-D deficiency

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Ask whether symptoms are diffuse or focal and whether weakness or bone pain came first. Clarify diet, sunlight, skin pigmentation, clothing, pregnancy, bariatric or bowel surgery, diarrhoea, kidney or liver disease and medicine exposure including anticonvulsants, glucocorticoids, tenofovir and repeated iron infusions. Record fractures, dental history, childhood deformity and family history. Sudden focal pain or inability to bear weight changes the encounter from deficiency assessment to possible structural failure.

Observe transfer from a chair, gait and stair ability. Test proximal power while accounting for pain, palpate ribs, pelvis, tibiae and metatarsals for bony tenderness and examine limb alignment. At a focal painful region, assess skin, deformity and distal neurovascular function and avoid repeated stress manoeuvres. Look for Chvostek or carpopedal spasm only as supportive signs; clinically important hypocalcaemia requires ECG and laboratory confirmation.

The basic biochemical panel defines the pathway. In nutritional deficiency, low vitamin D reduces calcium absorption, PTH rises, urinary phosphate loss increases and ALP reflects osteoblast response. Calcium can therefore look deceptively normal. Correct for albumin or measure ionised calcium when acute symptoms or protein disturbance make adjusted calcium unreliable. Check magnesium because depletion can prevent appropriate PTH secretion and make hypocalcaemia resistant to treatment.

Radiograph the site of focal pain in two planes and inspect for cortical lucency, insufficiency fracture, bowing and an alternative destructive lesion. Looser zones are transverse incomplete defects, often bilateral and symmetrical, rather than the ragged permeative destruction of malignancy. MRI is the preferred sensitive test for occult femoral-neck, sacral or pelvic stress injury and also maps marrow oedema. CT helps define cortex and operative anatomy but can miss early physiological stress response.

Give crutches, a frame or temporary non-weight-bearing when pain localises to a high-risk weight-bearing bone. Incomplete compression-side femoral-neck injury may be observed in selected cases, whereas tension-side, progressing or displaced lesions often need fixation; the metabolic defect must be treated in parallel. Use VTE assessment during reduced mobility. Fracture fixation in soft bone may need load-sharing and a rehabilitation plan that does not depend on unrealistic restrictions.

For adult nutritional vitamin-D deficiency needing loading, use a total dose near 300,000 units spread over six to ten weeks with colecalciferol, then maintenance 800 to 2,000 units daily according to cause and ongoing risk. Ensure adequate calcium intake and use supplements when diet is insufficient. Ordinary deficiency uses colecalciferol, not routine calcitriol. Advanced CKD, hypoparathyroidism, granulomatous disease, pregnancy and malabsorption require specialist selection and closer biochemical monitoring.

If phosphate remains low after vitamin-D and calcium status are addressed, obtain fasting simultaneous plasma and urine phosphate and creatinine. During true depletion the kidney should conserve phosphate; inappropriate excretion supports renal wasting and calculation of fractional excretion or TmP/GFR. Review medicines, urinalysis for generalized proximal tubular loss and FGF23-mediated disease. Localise a suspected mesenchymal tumour only after demonstrating the biochemical mechanism, using specialist functional and anatomical imaging.

Clinical improvement in strength may precede complete radiographic repair. ALP can initially rise as healing accelerates and then falls over months, so a single early value does not prove failure. Review calcium after loading, reassess phosphate, PTH, ALP and symptoms according to severity and investigate non-response rather than giving repeated empirical megadoses. When pain settles, rebuild hip and calf strength, balance and loading gradually while repeating imaging for high-risk incomplete fractures.

Key points

Osteomalacia is inadequate mineralisation of adult osteoid; high-yield clues are diffuse bone tenderness, proximal weakness, waddling gait and insufficiency or Looser-zone fractures.
First-line bloods are adjusted calcium, phosphate, alkaline phosphatase, PTH, 25-hydroxyvitamin D, magnesium, renal and liver profiles, interpreted as one physiological pattern.
Nutritional vitamin-D deficiency commonly produces low 25-hydroxyvitamin D, raised ALP and PTH and low phosphate, while adjusted calcium may remain low-normal through compensation.
First-line imaging of focal pain is site-specific radiography; use MRI when a femoral-neck, sacral, pelvic or other insufficiency fracture remains suspected despite normal films.
Protect weight bearing immediately across a painful high-risk femoral or pelvic site until an incomplete fracture has been excluded and orthopaedic stability is known.
For uncomplicated adult deficiency requiring rapid correction, a guideline loading total near 300,000 units of colecalciferol over six to ten weeks is followed by 800 to 2,000 units daily maintenance.
Do not prescribe phosphate blindly: persistent low phosphate requires fasting paired plasma and urine assessment to separate appropriate conservation from renal wasting.
Biochemical correction precedes potent antiresorptive treatment because denosumab or intravenous bisphosphonate can worsen hypocalcaemia in inadequately mineralised bone.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Low vitamin-D supply

Limited sunlight, concealing clothing, dark skin, housebound living, low dietary intake and malabsorption can reduce substrate for intestinal calcium and phosphate absorption.

Impaired activation

Advanced kidney disease reduces calcitriol generation, while severe liver disease and selected medicines can disrupt vitamin-D metabolism and compound mineral imbalance.

Renal phosphate wasting

Tubular disease, medicines, hereditary transport defects and excess FGF23 cause inappropriate urinary phosphate loss despite systemic depletion.

Drug and surgical causes

Anticonvulsants, tenofovir, repeated iron infusions with susceptible formulations, bariatric surgery and extensive bowel disease can create distinct vitamin-D or phosphate deficits.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Unmineralised osteoid
Osteoblasts lay down collagen matrix, but inadequate calcium-phosphate product prevents normal hydroxyapatite deposition, leaving compliant bone that bends and cracks under routine load.
2
Secondary hyperparathyroidism
Reduced calcium absorption stimulates PTH, which preserves serum calcium through skeletal resorption and renal phosphate loss while further compromising mineralisation.
3
Pseudofracture formation
Repeated stress across softened cortex produces transverse incomplete radiolucent defects with sclerotic margins, commonly at femoral neck, pubic rami, ribs and scapulae.
4
Muscle dysfunction
Vitamin-D and phosphate deficits impair proximal muscle performance, producing difficulty rising and a waddling gait that increases falls and fracture exposure.
5
Deformity under load
Prolonged untreated disease permits bowing of weight-bearing bones, altered hip mechanics and secondary joint degeneration, especially when onset predates skeletal maturity.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Diffuse bone tenderness

Pain elicited over ribs, pelvis, tibiae or metatarsals alongside generalized aching is more suggestive than isolated joint-line tenderness.

Proximal weakness

Difficulty rising without arms, climbing stairs or lifting the legs produces waddling gait and compounds fracture risk.

Looser pseudofracture

A transverse cortical lucency with a sclerotic margin, often symmetrical at characteristic sites, represents incomplete mineralisation-related stress failure.

Compensated calcium pattern

Low vitamin D with raised PTH and ALP plus reduced phosphate can coexist with normal adjusted calcium because PTH defends serum concentration.

Renal phosphate loss

Low plasma phosphate with urinary excretion that remains inappropriately high despite fasting depletion identifies a tubular or FGF23-driven mechanism.

High-risk focal pain

New groin, thigh or pelvic pain on standing indicates an insufficiency fracture until adequate imaging establishes safe loading.

Red flags requiring action

Focal groin or thigh pain, pain on axial loading or sudden loss of walking may represent an incomplete femoral-neck or subtrochanteric insufficiency fracture.
Multiple symmetrical Looser zones, marked deformity or rapidly worsening pain requires protected loading and specialist metabolic-bone and orthopaedic review.
Perioral tingling, carpopedal spasm, seizure, stridor or arrhythmia suggests clinically important hypocalcaemia requiring urgent ECG and biochemical correction.
Severe weakness, respiratory compromise, rhabdomyolysis or haemolysis with very low phosphate requires urgent monitored phosphate management and investigation.
Weight loss, anaemia, hypercalcaemia or a solitary destructive lesion is inconsistent with simple nutritional deficiency and raises malignancy or myeloma.
Persistent hypophosphataemia despite corrected vitamin D suggests renal phosphate wasting, Fanconi syndrome or FGF23-mediated tumour-induced osteomalacia.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line mineral and organ profileFirst stepFirst line
Why
Distinguish vitamin-D deficiency, calcium deficit, kidney disease and phosphate loss while identifying acute treatment hazards.
Interpretation and limitations
Interpret adjusted or ionised calcium, phosphate, ALP, PTH, vitamin D, magnesium, renal and liver tests together rather than acting on one result.
02
First-line focal radiographsFirst line
Why
Detect pseudofracture, complete fracture, deformity or a destructive alternative at the symptomatic site.
Interpretation and limitations
Normal films do not exclude early femoral-neck, sacral or pelvic insufficiency injury; maintain protection if clinical suspicion remains.
03
MRI for occult insufficiency injury
Why
Identify marrow oedema and incomplete fracture before cortical failure becomes visible on plain imaging.
Interpretation and limitations
MRI is the reference sensitive study for a persistently painful high-risk site and helps distinguish fracture from infiltrative marrow disease.
04
Fasting paired urine and plasma phosphate
Why
Determine whether hypophosphataemia reflects appropriate renal conservation or inappropriate urinary loss.
Interpretation and limitations
Calculate fractional excretion or TmP/GFR with specialist support; renal wasting redirects investigation toward tubular disease, medicines or FGF23 excess.
05
Cause-directed malabsorption and tumour tests
Why
Identify coeliac disease, pancreatic or bowel disease, proximal tubulopathy or tumour-induced osteomalacia when routine replacement fails.
Interpretation and limitations
Choose tests from history and biochemical mechanism; indiscriminate tumour scanning before proving phosphate wasting creates incidental findings.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Osteoporosis

Fragility fracture with otherwise normal calcium, phosphate and alkaline phosphatase suggests reduced bone quantity rather than widespread defective mineralisation.

Inflammatory myopathy

True proximal weakness with raised creatine kinase and little bony tenderness points toward muscle inflammation, although both disorders can coexist.

Myeloma or metastatic disease

Focal night pain, lytic lesions, anaemia, renal impairment, hypercalcaemia or monoclonal protein requires oncological investigation before attributing symptoms to deficiency.

Primary hyperparathyroidism

Raised adjusted calcium with inappropriately high PTH and low phosphate indicates autonomous parathyroid activity rather than compensatory PTH from vitamin-D deficiency.

Hypophosphatasia

Persistently low rather than raised alkaline phosphatase, early tooth loss and recurrent metatarsal or atypical femoral fractures suggest this inherited mineralisation disorder.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Immediate structuralProtect a painful weak boneFirst stepFocal weight-bearing pain, loss of walking or a pseudofracture raises concern for impending completion.

1Stop provocative loading, document limb alignment and neurovascular findings and provide safe mobility aids.
2Obtain radiographs in two planes and use MRI promptly when a high-risk occult fracture remains possible.
3Refer tension-side, progressing, displaced or mechanically unsafe femoral lesions urgently for fixation assessment.
4Treat mineral deficiency and perform VTE-risk assessment alongside rather than after mechanical care.

02First-line biochemicalDefine the missing substrateFirst lineDiffuse pain, proximal weakness or insufficiency fracture suggests mineralisation failure.

1Measure adjusted calcium, phosphate, ALP, PTH, vitamin D, magnesium and renal and liver function.
2Review diet, sunlight, bowel or bariatric disease, kidney disease and medicine exposures.
3Use ECG and monitored acute replacement for symptomatic severe calcium or phosphate disturbance.
4Avoid antiresorptive treatment until hypocalcaemia and important vitamin-D deficiency have been corrected.

03Nutritional treatmentLoad then maintain vitamin DDeficiency is confirmed without a disorder requiring activated vitamin-D or specialist phosphate therapy.

1Provide a colecalciferol loading total near 300,000 units over six to ten weeks when rapid correction is needed.
2Ensure adequate calcium intake and prescribe supplementation when diet cannot meet requirements.
3Continue 800 to 2,000 units colecalciferol daily for persistent risk, adjusting to cause and local guidance.
4Check calcium after loading and follow phosphate, ALP, PTH, strength and fracture pain to document recovery.

04RefractoryInvestigate phosphate and absorptionSymptoms, ALP or low phosphate persist despite verified replacement and adherence.

1Confirm dosing, preparation, adherence, calcium intake and malabsorption rather than repeating blind loading.
2Obtain fasting paired plasma and urine phosphate and calculate renal handling with specialist advice.
3Test for generalized tubulopathy, medicine causes and FGF23-mediated disease according to the result.
4Coordinate metabolic-bone, renal, endocrine and orthopaedic care for persistent fractures or suspected tumour-induced disease.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Replenishes vitamin-D stores quickly enough to support calcium absorption, mineralisation and treatment of secondary hyperparathyroidism.

Colecalciferol loading for adult deficiency

Use an oral regimen totalling about 300,000 units over six to ten weeks, such as 50,000 units weekly for six weeks, then change to maintenance according to current local guidance.

Check calcium and renal status, avoid duplicated over-the-counter products and seek specialist advice for pregnancy, granulomatous disease, stones, severe kidney disease or malabsorption.

Prevents recurrence while osteoid and insufficiency fractures complete their slower structural recovery.

Colecalciferol maintenance

Continue 800 to 2,000 units orally each day after loading when an ongoing adult risk remains, individualising for diet, absorption, body size and specialist advice.

Do not escalate indefinitely from one low result; confirm adherence and mechanism and monitor calcium when toxicity or altered metabolism is possible.

Supplies calcium substrate when food intake cannot support correction and PTH remains driven by calcium deficit.

Calcium supplementation when dietary intake is inadequate

Select a preparation providing enough elemental calcium to bring total daily intake near the locally recommended range, divided when larger doses are required and separated from interacting medicines.

Estimate dietary intake first and review constipation, kidney stones, hypercalciuria, renal impairment and interactions with levothyroxine, iron and some antibiotics.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Insufficiency fracture

Femoral-neck, pelvic, sacral, rib and metatarsal failure can progress from an incomplete stress reaction to displacement if loading continues.

Skeletal deformity

Bowing, coxa vara, kyphosis and altered limb alignment cause mechanical pain, inefficient gait and secondary osteoarthritis after biochemical healing.

Falls and deconditioning

Proximal weakness reduces transfers and balance; immobilisation then accelerates muscle loss, thrombosis risk and loss of independence.

Replacement-induced disturbance

Unmonitored high-dose vitamin D or calcium can cause hypercalcaemia, hypercalciuria and renal injury, especially in granulomatous disease or renal impairment.

Missed phosphate-wasting tumour

Assuming all osteomalacia is nutritional can delay localisation of an FGF23-secreting mesenchymal tumour while fractures and deformity accumulate.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Reassess focal pain and loading ability early; worsening pain across a femoral neck or weight-bearing cortex requires repeat imaging and orthopaedic review.
Check adjusted calcium approximately one month after a loading course, earlier with symptoms, severe baseline disturbance or high-risk comorbidity.
Trend phosphate, ALP, PTH, renal function and clinical strength; interpret an early ALP rise in the context of healing rather than alone.
Confirm the patient has changed from loading to maintenance and is not simultaneously using multiple high-dose preparations.
Repeat radiographs or MRI for a high-risk incomplete fracture before unrestricted impact or return to heavy work.
Escalate persistent low phosphate or non-response for fasting renal-handling tests, malabsorption work-up and specialist metabolic-bone review.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Normal calcium can mislead

Secondary hyperparathyroidism can maintain circulating calcium while phosphate falls and skeletal mineralisation continues to fail.

A pseudofracture is real failure

Looser zones are incomplete stress fractures and require mechanical protection as well as biochemical replacement.

ALP may lag recovery

Bone formation markers can remain high or transiently increase while accumulated unmineralised osteoid finally mineralises.

Phosphate needs a mechanism

Replacement without determining renal handling can mask an ongoing tubular or FGF23-driven loss and cause avoidable complications.

MRI protects the normal radiograph

Occult femoral-neck or sacral insufficiency injury may be structurally important before a cortical line appears.

Antiresorption can worsen deficit

Potent suppression of skeletal calcium release can precipitate severe hypocalcaemia when mineral substrate has not been restored.

11Common pitfallsFrequent interpretation and management errors.

01
Reassuring a patient with focal groin pain because the first radiograph is normal.
02
Calling diffuse pain osteoporosis without checking phosphate, ALP, PTH and vitamin-D physiology.
03
Giving repeated empirical megadoses when low phosphate or raised ALP persists despite verified correction.
04
Using calcitriol routinely for nutritional deficiency or prescribing phosphate without defining renal handling.
05
Starting denosumab or intravenous bisphosphonate before correcting hypocalcaemia and material vitamin-D deficiency.
06
Allowing unrestricted weight bearing through a painful Looser zone while waiting for laboratory improvement.