Vitamin D deficiency and osteomalacia

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

Vitamin D supports intestinal calcium and phosphate absorption and thereby skeletal mineralisation. Low exposure or absorption first provokes PTH, which maintains serum calcium by increasing bone resorption and renal phosphate loss; calcium can therefore appear normal while phosphate falls and alkaline phosphatase rises. Osteomalacia presents with diffuse bone tenderness, lower back, rib, pelvic or leg pain, waddling gait and proximal muscle weakness, often mistaken for fibromyalgia, arthritis or frailty. Insufficiency fractures or Looser zones can occur. Osteoporosis, by contrast, is reduced bone strength with normally mineralised matrix and is often silent until fracture. They can coexist, but treating osteomalacia with a potent antiresorptive before correcting calcium-vitamin D physiology may worsen hypocalcaemia.

NICE CKS uses 25-hydroxyvitamin D to diagnose deficiency in an appropriate clinical context and recommends a finite loading regimen followed by maintenance for people needing rapid correction. Choose a licensed preparation where possible, specify daily versus weekly frequency clearly and assess adherence and absorption before repeating high-dose courses. Treat the cause: coeliac disease, pancreatic or biliary disease, bariatric anatomy, anticonvulsant exposure, severe liver disease and advanced CKD may need specialist modification. Native colecalciferol or ergocalciferol replenishes stores; activated analogues are not routine deficiency treatment and create greater hypercalcaemia risk. Calcium supplementation is appropriate when dietary intake is inadequate or acute hypocalcaemia requires it, not automatically for every low vitamin D result. Review pain, strength and alkaline phosphatase over months because skeletal healing lags behind the vitamin concentration.

Key points

Vitamin D deficiency is a biochemical state; osteomalacia is defective mineralisation with bone pain, proximal weakness, fractures and supportive biochemical or imaging features.
Test people with suspected osteomalacia, hypocalcaemia, relevant malabsorption or another result that will change management rather than screening low-risk adults indiscriminately.
25-hydroxyvitamin D is the usual status test; 1,25-dihydroxyvitamin D can be normal or raised in nutritional deficiency and is not a routine screening test.
Osteomalacia commonly produces raised alkaline phosphatase, secondary hyperparathyroidism and low phosphate, while calcium may remain normal until deficiency is advanced.
Risk reflects reduced ultraviolet exposure, darker skin, covering, low dietary intake, ageing skin, obesity, pregnancy, malabsorption, bariatric surgery, liver-kidney disease and enzyme-inducing medicines.
Use a defined loading course when rapid correction is needed, then switch explicitly to maintenance; repeated loading without review is a common route to toxicity.
Check calcium after pharmacological replacement because treatment can unmask primary hyperparathyroidism or cause hypercalcaemia through excessive dosing.
SACN advises a reference nutrient intake of 10 micrograms daily for the general population aged four and over, with public-health access and prescribing rules applied locally.

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

Low vitamin D exposure

Limited sunlight exposure, low dietary intake and reduced skin synthesis lower vitamin D stores, particularly when several risks coexist.

Malabsorption or altered anatomy

Coeliac, pancreatic or biliary disease and bariatric surgery reduce absorption of fat-soluble vitamin D and sometimes calcium.

Impaired metabolism or medicine effect

Severe liver disease, advanced kidney disease and enzyme-inducing medicines alter vitamin D processing or increase its breakdown.

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

1
Calcium and phosphate absorption falls
Low vitamin D action reduces intestinal mineral uptake, even when serum calcium remains initially within range.
2
PTH rises compensatorily
Parathyroid hormone preserves serum calcium through bone resorption and renal conservation while increasing urinary phosphate loss, maintaining extracellular calcium partly at skeletal expense.
3
Bone matrix remains under-mineralised
Osteoid is produced but lacks adequate calcium-phosphate mineral, making bone soft, painful and mechanically weak while the condition remains active.
4
Muscle function deteriorates
Deficiency contributes to proximal weakness and impaired gait, adding falls risk to the underlying skeletal fragility.

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

Osteomalacic pain

Diffuse symmetrical bone pain and tenderness involving ribs, pelvis, lower back or legs, with difficulty standing or climbing stairs, suggests impaired mineralisation rather than isolated low density.

Proximal myopathy

Waddling gait, chair-rise difficulty and hip-girdle weakness can be prominent and increase falls even before a fracture is recognised.

Secondary PTH response

Raised PTH, raised alkaline phosphatase and low phosphate with low vitamin D supports physiologically significant deficiency, although liver ALP and CKD need separation.

Malabsorption phenotype

Chronic diarrhoea, weight loss, iron deficiency, coeliac risk, pancreatic disease or bariatric surgery makes poor absorption likely and changes dose and follow-up needs.

Deficiency complication

Insufficiency fracture, tetany or severe weakness indicates clinically important disease and warrants cause investigation rather than over-the-counter maintenance advice alone.

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
Serum 25-hydroxyvitamin DFirst step
Why
Measure body vitamin D status in a person whose symptoms, biochemical pattern or risk makes the result actionable.
Interpretation and limitations
Use the local assay and NICE CKS categories. A low value supports deficiency but osteomalacia requires clinical and mineralisation evidence, not the concentration alone.
02
Calcium, phosphate and alkaline phosphatase
Why
Identify mineralisation disturbance and establish safety before replacement.
Interpretation and limitations
Low phosphate and raised bone-derived ALP support osteomalacia; calcium may be preserved by PTH. Clarify liver ALP with other liver tests when the source is uncertain.
03
PTH, magnesium and renal function
Why
Assess compensation, refractory electrolyte deficiency and CKD-related mineral bone disease.
Interpretation and limitations
Raised PTH supports secondary physiology; low magnesium may worsen hypocalcaemia, while eGFR below 30 changes active vitamin D handling and specialist thresholds.
04
Targeted malabsorption assessment
Why
Find why appropriate replacement fails or why deficiency is unexpectedly severe or recurrent.
Interpretation and limitations
Coeliac serology with total IgA, nutritional indices and cause-directed gastrointestinal tests guide treatment; negative serology is unreliable after gluten avoidance or IgA deficiency.
05
Radiograph of painful or load-bearing site
Why
Detect insufficiency fracture, Looser zone or another structural explanation for focal pain.
Interpretation and limitations
A pseudofracture supports osteomalacia and needs activity and orthopaedic advice; normal plain imaging does not exclude early mineralisation disease.
06
DXA with fracture-risk assessment
Why
Quantify coexisting low bone density after recognising that DXA cannot distinguish osteoporosis from osteomalacia.
Interpretation and limitations
Low BMD may improve after mineralisation is restored. Use clinical fracture risk and avoid assigning primary osteoporosis solely from density during untreated osteomalacia.

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

Osteoporosis

Osteoporosis has reduced bone strength with normally mineralised matrix and is often painless until fracture, whereas osteomalacia causes pain and weakness.

Inflammatory or mechanical pain

Arthritis, fibromyalgia and degenerative disease can cause diffuse pain, but lack the coherent mineral, PTH and alkaline-phosphatase pattern.

Primary hyperparathyroidism

High or inappropriately non-suppressed PTH with hypercalcaemia suggests gland autonomy rather than a compensatory response to vitamin D deficiency.

Renal mineral-bone disorder

Advanced kidney disease alters phosphate, active vitamin D and PTH together, requiring renal rather than routine nutritional management.

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

01DiagnoseLink symptoms to mineral physiologyFirst stepBone pain, weakness, fracture or biochemical abnormality raises possible osteomalacia.

1Assess pain distribution, gait, proximal strength, falls, diet, sunlight, skin exposure, malabsorption, medicines and kidney-liver disease.
2Measure 25-hydroxyvitamin D with calcium, phosphate, ALP, PTH, magnesium and renal function and image focal skeletal pain.
3Classify simple deficiency versus clinical osteomalacia or CKD-mineral disease, and refer unexplained, severe or treatment-resistant patterns before repeated loading.

02ReplaceCorrect deficiency and maintain storesDeficiency is confirmed and rapid treatment is clinically indicated.

1Choose a NICE CKS and local-formulary fixed loading regimen with a clearly documented cumulative course and administration frequency.
2Ensure adequate dietary calcium or supplement when indicated, manage magnesium and transition to a stated maintenance dose when loading finishes.
3Check calcium at the appropriate safety interval, assess adherence and symptoms, and investigate malabsorption or another diagnosis if the expected biochemical response fails.

03Restore boneManage osteomalacia and fracture riskDeficiency has caused weakness, pseudofracture or broader mineralisation disease.

1Protect painful load-bearing bone, arrange falls and physiotherapy support and seek orthopaedic advice for incomplete or completed fracture.
2Treat the underlying absorption, dietary, medicine, liver or renal driver and allow time for alkaline phosphatase, pain and strength to recover.
3Reassess fracture risk after mineral physiology improves and start osteoporosis therapy only when still indicated with calcium and vitamin D replete enough for safety.

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

Replenishes vitamin D stores so intestinal calcium-phosphate absorption and skeletal mineralisation can recover.

Colecalciferol

For treatment, use a locally approved finite loading regimen drawn from NICE CKS, then move to the documented daily maintenance dose; public-health prevention uses the current SACN intake advice rather than repeated loading.

Daily and weekly products create frequency errors, and prolonged high exposure causes hypercalcaemia and renal injury. Review calcium, renal disease, granulomatous disease, pregnancy and interacting medicines; investigate non-response before reloading.

Supports mineralisation when dietary calcium is inadequate and provides oral continuation after acute hypocalcaemia.

Calcium supplement

Use a divided elemental-calcium amount selected for measured dietary shortfall, hypocalcaemia and the local bone protocol, documenting the salt and elemental content.

Constipation, stones and medicine interactions occur. Routine supplementation is unnecessary when intake is sufficient, and CKD or hypercalciuria requires specialist caution.

Bypasses impaired renal activation when advanced CKD produces persistent mineral bone symptoms and secondary hyperparathyroidism.

Activated vitamin D in advanced CKD

Use alfacalcidol or calcitriol only after renal-specialist assessment, once native vitamin D deficiency is addressed, and titrate under the CKD-mineral bone protocol.

Hypercalcaemia and hyperphosphataemia can accelerate vascular calcification. This is not an interchangeable or routine substitute for colecalciferol in nutritional deficiency.

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

Insufficiency fracture

Poorly mineralised bone can develop Looser zones and fractures through ordinary loading, often in pelvis, ribs or lower limbs.

Falls and disability

Proximal weakness, waddling gait and bone pain reduce mobility, increasing falls, dependence and deconditioning until mineral and muscle function recover.

Hypocalcaemia

Severe deficiency or antiresorptive treatment before mineral correction can overwhelm PTH compensation and lower extracellular calcium.

Persistent secondary hyperparathyroidism

Ongoing malabsorption, poor adherence or uncorrected calcium deficiency sustains PTH elevation and continued skeletal turnover despite repeated vitamin D courses.

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

Check adjusted calcium at the locally recommended interval after pharmacological treatment and urgently if thirst, vomiting, constipation or confusion develops.
Follow pain, gait, chair-rise and falls as clinical outcomes; a corrected laboratory value without functional recovery should trigger diagnostic review.
Trend ALP, phosphate and PTH in osteomalacia because bone healing can take longer than restoration of 25-hydroxyvitamin D.
Repeat vitamin D selectively after the expected steady-state interval in severe disease, malabsorption, persistent symptoms or suspected non-adherence rather than routinely overtesting everyone.
Ensure the loading prescription has an automatic stop or switch to maintenance so repeats are not generated indefinitely.

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

Normal calcium can be compensated

Secondary PTH can preserve plasma calcium by sacrificing phosphate and bone mineral. Normal calcium therefore does not rule out symptomatic osteomalacia.

DXA cannot see mineral quality

Low density occurs in both osteoporosis and osteomalacia. The biochemical pattern and symptoms decide whether matrix quantity or mineralisation is the dominant problem.

One-alpha level misleads

PTH stimulation can maintain or raise 1,25-dihydroxyvitamin D during nutritional deficiency. Measure 25-hydroxyvitamin D for stores unless a specialist question differs.

ALP recovery may lag

Bone turnover can transiently remain high while previously unmineralised matrix heals. Interpret the direction with symptoms and phosphate rather than expecting instant normalisation.

Loading needs an endpoint

A high-dose course is a finite correction tool. Explicit transition to maintenance prevents an accidental chronic regimen and vitamin D toxicity.

11Common pitfallsFrequent interpretation and management errors.

01
Calling every low vitamin D concentration osteomalacia without bone symptoms or mineralisation evidence.
02
Requesting 1,25-dihydroxyvitamin D as the routine test of nutritional stores.
03
Starting intravenous antiresorptive therapy before correcting severe vitamin D deficiency and hypocalcaemia risk.
04
Repeating loading courses without checking adherence, malabsorption, calcium and the original indication.
05
Assuming a low DXA T-score distinguishes osteoporosis from untreated osteomalacia.
06
Using activated vitamin D for simple deficiency without the tighter calcium-phosphate monitoring it requires.