Endocrine

Vitamin D deficiency: screening, treatment, and counseling

Clinical Overview and When to Suspect Vitamin D Deficiency

— Deficiency: serum 25-hydroxyvitamin D (25-OH D) <20 ng/mL

— Insufficiency: 20–29 ng/mL

— Sufficiency: ≥30 ng/mL (Endocrine Society) or ≥20 ng/mL (IOM for general bone health)

— Toxicity: typically >100 ng/mL with hypercalcemia

— Drives secondary hyperparathyroidism, osteomalacia in adults, rickets in children

— Contributes to falls and fragility fractures in elders

— Amplifies hypocalcemia in CKD, post-bariatric, malabsorption states

— Diffuse bone pain, proximal muscle weakness, waddling gait

— Unexplained ↑ alkaline phosphatase with low/normal calcium and phosphorus

— Recurrent low-trauma fractures or osteoporosis on DEXA

— Falls in elderly, especially institutionalized patients

— Malabsorption: celiac, IBD, cystic fibrosis, post-Roux-en-Y bypass

— Chronic glucocorticoids, anticonvulsants (phenytoin, phenobarbital), rifampin, antiretrovirals

— CKD stage 3–5, nephrotic syndrome, cholestatic liver disease

— Dark skin, veiling/limited sun exposure, exclusively breastfed infants without supplementation

— Obesity (BMI ≥30) — sequestration in adipose

— Insufficient evidence (I statement) to screen asymptomatic, community-dwelling, non-pregnant adults

— Do not order 25-OH D as a "routine" wellness lab

Board pearl: On Step 3, the screening question is a trap — the right answer for an asymptomatic, healthy 45-year-old is usually "do not screen", while a frail 78-year-old after a hip fracture or a patient post-gastric bypass earns a 25-OH D level. Anchor your decision to risk factors, not to general "wellness."

Definition (Endocrine Society / IOM thresholds):

Why it matters in Step 3 practice:

When to suspect deficiency (clinical triggers):

USPSTF stance (high-yield):

Endocrine Society stance: screen only at-risk populations (above list)

Presentation Patterns and Key History

— Diffuse, poorly localized bone pain — pelvis, ribs, spine, proximal long bones

— Proximal muscle weakness — difficulty rising from chair, climbing stairs, waddling gait

— Pseudofractures (Looser zones) on imaging

— Bone tenderness to sternum/tibia pressure

— Delayed fontanelle closure, craniotabes, frontal bossing

— Rachitic rosary, Harrison groove, genu varum or valgum

— Delayed motor milestones, dental enamel defects

— Hypocalcemic seizures in infants (especially exclusively breastfed, dark-skinned)

— Increased fall risk independent of bone density

— Low-trauma vertebral, hip, distal radius fractures

— Fatigue, depressive symptoms (causality unproven)

— Worse outcomes in some chronic diseases — do not present as treatment indication on boards

— Sun exposure habits, sunscreen use, latitude, occupation (indoor/night shift)

— Dietary intake: fatty fish, fortified dairy/cereals, egg yolks

— Veganism or strict vegetarianism (vit D2 only sources)

— Bariatric surgery type and date — Roux-en-Y and biliopancreatic diversion cause fat-soluble vitamin malabsorption

— Medications: glucocorticoids, antiepileptics, antifungals, HIV meds, cholestyramine, orlistat

— GI symptoms suggestive of celiac, IBD, pancreatic insufficiency

— Skin pigmentation, cultural dress, residence in nursing home

Key distinction: Rickets = growing skeleton (pediatric) with defective growth plate mineralization; osteomalacia = adult skeleton with defective osteoid mineralization. Same biochemistry, different histology — the boards love this dyad.

Asymptomatic (most common): detected only via screening of at-risk patient or workup of osteoporosis, hypocalcemia, or elevated PTH

Musculoskeletal pattern (osteomalacia in adults):

Pediatric rickets pattern:

Falls and fractures:

Extraskeletal associations (less exam-emphasized but appear):

Key history to elicit:

Physical Exam Findings and Functional Assessment

— Often completely normal — most deficient adults have no findings

— Sallow appearance, frailty markers in chronically deficient elders

— Proximal muscle weakness — test with sit-to-stand from chair without arms, 30-second chair stand

— Waddling (Trendelenburg-like) gait from hip girdle weakness

— Bone tenderness — palpate sternum, anterior tibia, iliac crests

— Chvostek and Trousseau signs if profound hypocalcemia coexists

— Kyphosis from vertebral compression in advanced osteomalacia

— Timed Up and Go (TUG) >12 seconds → increased fall risk

— 30-second chair stand, gait speed <0.8 m/s

— Orthostatic vitals

— Vision screen, foot exam, footwear review

— Home hazard inquiry

— Craniotabes — ping-pong-ball skull on parietal pressure

— Rachitic rosary — beading at costochondral junctions

— Harrison groove — horizontal depression along diaphragm insertion

— Widened wrists/ankles, bowing of legs once weight-bearing

— Hypotonia, "frog-leg" posture in infants

— Short stature, dental caries/enamel hypoplasia in children

— Signs of malabsorption: glossitis, cheilosis, steatorrhea, dermatitis herpetiformis (celiac)

— Cushingoid habitus (glucocorticoid use)

— Post-bariatric surgical scars

Step 3 management: When an older adult presents with a fall, your exam must include gait/balance, orthostatics, vision, cognition, medication review, AND a vitamin D risk assessment — supplementation in deficient or insufficient elders reduces fall risk and is part of the AGS/CDC STEADI bundle. Document each component to satisfy quality measures.

General exam:

Musculoskeletal:

Functional/falls assessment (essential in elderly Step 3 vignettes):

Pediatric exam (rickets):

Associated findings prompting workup:

Diagnostic Workup — Initial Labs

— Reflects total body stores (half-life ~2–3 weeks)

— Includes both D2 and D3 contributions

— Do not order 1,25-dihydroxyvitamin D for screening or routine deficiency

— 1,25-(OH)2 D is short half-life, tightly regulated, often normal or high in deficiency due to compensatory PTH-driven 1α-hydroxylation

— Reserve 1,25-(OH)2 D for suspected granulomatous disease (sarcoid, TB, lymphoma), CKD evaluation, or unexplained hypercalcemia

— Serum calcium (total + albumin or ionized)

— Phosphorus

— Intact PTH — typically elevated (secondary hyperPTH) in true deficiency

— Alkaline phosphatase — elevated in osteomalacia/rickets

— Magnesium — hypomagnesemia blunts PTH and impairs vit D response

— Creatinine/eGFR — defines renal contribution

— 24-hour urine calcium — low in deficiency, helps differentiate later

— ↓ 25-OH D, ↓/normal Ca, ↓ phosphorus, ↑ PTH, ↑ alk phos, ↑ urine cAMP

— Tissue transglutaminase IgA + total IgA (celiac)

— Fecal elastase (pancreatic insufficiency)

— CBC, ferritin, B12, folate, INR (other deficiencies)

— LC-MS/MS is gold standard; immunoassays may underestimate D2

— Obesity falsely lowers measured 25-OH D due to volumetric dilution — interpret modestly low values cautiously in BMI ≥30

Board pearl: A vignette with low Ca, low phosphate, high alk phos, high PTH, normal creatinine = vitamin D deficiency / osteomalacia until proven otherwise. Compare with primary hyperparathyroidism (high Ca, low phosphate, high PTH) and hypoparathyroidism (low Ca, high phosphate, low PTH) — the phosphate and PTH directions resolve most stem confusion.

Test of choice: serum 25-hydroxyvitamin D (25-OH D)

Companion labs at diagnosis (deficiency workup panel):

Expected biochemistry of classic deficiency:

If malabsorption suspected:

Assay caveats:

Diagnostic Workup — Advanced or Confirmatory Studies

— Plain radiographs of pelvis, femur, ribs: Looser zones (pseudofractures) — transverse radiolucent bands perpendicular to cortex, classically along medial femoral neck, pubic rami, scapula

— Generalized osteopenia, coarsened trabeculae

— Pediatric: widened, cupped, frayed metaphyses of distal radius/ulna, knees

— Bone scan: multiple symmetric uptake foci ("hot spots") at pseudofractures

— Indicated if osteoporosis suspected or fragility fracture present

— Low BMD common but not specific — treat deficiency before interpreting fully

— Recheck DEXA 1–2 years after repletion if therapy decisions hinge on it

— Gold standard for osteomalacia — increased unmineralized osteoid with prolonged mineralization lag time on tetracycline labeling

— Reserved for diagnostic uncertainty, especially atypical cases

— Persistently low 25-OH D despite adequate supplementation → check adherence, malabsorption, drug interactions, obesity, nephrotic loss

— Hypercalcemia with low/normal 25-OH D and high 1,25-(OH)2 D → granulomatous disease (chest CT, ACE level, biopsy)

— Hypophosphatemia disproportionate to deficiency → consider tumor-induced osteomalacia (FGF23), X-linked hypophosphatemia, Fanconi syndrome

— Failure of supplementation in a child → hereditary vitamin D-resistant rickets (VDR mutation) vs 1α-hydroxylase deficiency (vit D-dependent rickets type 1)

— Early-onset, familial rickets

— Hypophosphatemic rickets with normal 25-OH D

— Refractory disease despite confirmed adherence

Key distinction: Pseudofractures (Looser zones) are pathognomonic-ish for osteomalacia and differ from stress fractures: bilateral, symmetric, perpendicular to cortex, in classic locations. Stress fractures are typically unilateral, in active/athletic patients, along lines of mechanical load.

Imaging in suspected osteomalacia/rickets:

DEXA scan:

Bone biopsy (rarely on boards):

When to extend the differential workup:

Genetic/specialty referral indications:

Risk Stratification and Management Logic

— <20 ng/mL → treat with repletion course

— 20–29 ng/mL with risk factors (osteoporosis, malabsorption, elderly faller) → treat

— 20–29 ng/mL low-risk asymptomatic adult → maintenance dose ± lifestyle, no aggressive repletion needed

— ≥30 ng/mL → no treatment unless ongoing risk for deficiency

— Stop/limit offending drugs where possible (review anticonvulsants, glucocorticoids, orlistat)

— Treat underlying malabsorption (gluten-free diet, pancreatic enzyme replacement)

— Correct hypomagnesemia first — repletion fails without it

— Counsel on safe sun exposure (10–15 min midday on arms/face, not as a primary strategy due to skin cancer risk)

— D3 (cholecalciferol) preferred over D2 (ergocalciferol) for sustained levels

— Daily dosing equally effective and safer than mega-bolus dosing

— Avoid annual mega-doses (≥300,000–500,000 IU) — paradoxically increase fall and fracture risk in elders (key trial finding)

— Recheck 25-OH D after 3 months of repletion

— Once sufficient, transition to maintenance and recheck annually in high-risk patients

— CKD stage 4–5 — coordinate with nephrology, may need active D analog (calcitriol, paricalcitol)

— Post-bariatric — often require D3 50,000 IU weekly indefinitely

— Chronic glucocorticoids — higher maintenance dose, often 2000 IU/day

Step 3 management: A patient on long-term prednisone for rheumatoid arthritis should receive calcium 1000–1200 mg/day + vitamin D 800–2000 IU/day plus bone density screening and bisphosphonate if at moderate–high fracture risk per ACR guidelines — bundle these orders together rather than treating components in isolation.

Step 1 — Confirm deficiency category and risk:

Step 2 — Identify and address modifiable contributors:

Step 3 — Choose formulation and dose (see chunk 7):

Step 4 — Set follow-up:

Risk categories driving more aggressive repletion:

Pharmacotherapy — First-Line Regimens

— Vitamin D3 (cholecalciferol) 50,000 IU PO weekly × 8 weeks, then maintenance

— Alternative: D3 6000 IU PO daily × 8 weeks

— Ergocalciferol (D2) 50,000 IU weekly × 8 weeks is acceptable but less potent per IU

— Recheck 25-OH D at 3 months; if still <30 ng/mL, repeat 8-week course

— Adults 19–70: 600 IU/day (RDA), tolerable to 1500–2000 IU/day

— Adults >70: 800 IU/day (RDA), commonly 1000–2000 IU/day

— Obese, malabsorption, chronic glucocorticoid, antiepileptic users: 2–3× standard dose (often 50,000 IU monthly to weekly)

— Infants (breastfed or <1 L/day formula): 400 IU/day from birth (AAP)

— Children/adolescents: 600 IU/day RDA; deficiency treated with 2000 IU/day × 6 weeks or 50,000 IU weekly × 6 weeks (age-dependent)

— Co-prescribe 1000–1200 mg elemental calcium/day (diet preferred over supplements) — calcium supplements alone may modestly increase CV risk; use diet first

— Avoid high-dose calcium supplements in patients with nephrolithiasis history

— Calcitriol (1,25-(OH)2 D3) — for CKD stage 4–5, hypoparathyroidism, 1α-hydroxylase deficiency

— Paricalcitol, doxercalciferol — secondary hyperPTH in dialysis patients

— Risk: hypercalcemia, hyperphosphatemia — monitor closely

— Take with a fat-containing meal (fat-soluble)

— OTC availability — emphasize dose/formulation accuracy

Board pearl: Cholecalciferol (D3) is the preferred OTC choice because of longer half-life and more efficient raising of 25-OH D vs ergocalciferol (D2). The exception is patients who require a prescription-only formulation or have a contraindication to D3-source (rare).

Repletion (deficient adults, 25-OH D <20 ng/mL):

Maintenance dosing (after sufficiency achieved):

Pediatric:

Calcium pairing:

Active vitamin D analogs (specialist territory):

Adherence counseling:

Expanded Pharmacology and Drug–Disease Considerations

— Phenytoin, phenobarbital, carbamazepine

— Rifampin, isoniazid

— Efavirenz, some protease inhibitors

— Glucocorticoids (multifactorial — also impair Ca absorption, increase urinary loss)

— St. John's wort

— Cholestyramine, colestipol (bile acid sequestrants)

— Orlistat

— Mineral oil

— PPIs reduce calcium carbonate absorption (give calcium citrate instead)

— Thiazide diuretics + vitamin D → ↑ risk of hypercalcemia (reduced urinary Ca excretion)

— Digoxin + hypercalcemia from vit D toxicity → arrhythmia risk

— CKD stage 3: correct nutritional deficiency with D3 first; recheck PTH

— CKD stage 4–5/dialysis: add active vit D analog (calcitriol/paricalcitol) for secondary hyperPTH per KDIGO; monitor Ca, phosphate, PTH q1–3 months

— Granulomatous disease (sarcoidosis, TB): macrophages express 1α-hydroxylase autonomously → cautious supplementation, may precipitate hypercalcemia; target lower 25-OH D (20–30 ng/mL)

— Primary hyperparathyroidism with vit D deficiency: still safe and recommended to replete — does not worsen hypercalcemia in most; improves PTH

— Nephrolithiasis (calcium stones): vit D repletion is not contraindicated; monitor 24-h urine Ca; thiazide if hypercalciuric

— Hypercalcemia, hypercalciuria, nephrocalcinosis, AKI

— Anorexia, nausea, polyuria, polydipsia, constipation

— Management: stop vitamin D and calcium, IV saline, loop diuretic, glucocorticoids (decrease intestinal Ca absorption), bisphosphonate if severe

CCS pearl: In a hospitalized hypercalcemic patient with sarcoidosis or lymphoma, advance the clock after ordering IV normal saline + prednisone, hold all vitamin D/calcium, and consult nephrology if AKI or refractory Ca >14 mg/dL. Recheck Ca q6h initially.

Drugs that lower 25-OH D (induce CYP24A1 / CYP3A4 catabolism):

Drugs that impair absorption:

Drugs causing hypervitaminosis-like effects:

Disease-specific dosing pearls:

Toxicity (25-OH D >100–150 ng/mL):

Special Populations — Elderly and Renal/Hepatic Impairment

— Highest-yield Step 3 group — community-dwelling and institutionalized elders frequently deficient

— Skin synthesis decreases ~75% by age 70

— AGS recommends 800 IU/day vitamin D for community-dwelling elders at high fall risk plus deficient/insufficient 25-OH D

— Repletion reduces falls modestly; avoid annual mega-bolus dosing — increases falls/fractures (Sanders trial, 500,000 IU bolus harm)

— Combine with calcium 1200 mg/day (diet-first), weight-bearing exercise, home safety eval, vision correction, medication review (deprescribe sedatives, anticholinergics)

— Screen for osteoporosis: DEXA in women ≥65, men ≥70 (or earlier with risk factors); treat with antiresorptive if T-score ≤ −2.5 or fragility fracture

— Stage 1–2: treat like general population

— Stage 3–5: check 25-OH D, calcium, phosphate, PTH per KDIGO

— Repletion of nutritional deficiency with D3 first

— If PTH remains elevated and 25-OH D adequate → active analog (calcitriol/paricalcitol)

— Monitor for hypercalcemia and hyperphosphatemia; phosphate binders as needed

— Dialysis patients: managed by nephrology; cinacalcet sometimes added for severe secondary hyperPTH

— Avoid high-dose vit D bolus in CKD without monitoring

— Liver performs 25-hydroxylation — severe cirrhosis impairs activation

— Cholestatic disease (PBC, PSC) → fat-soluble vitamin malabsorption

— Use D3 with bile acid–enhancing strategies (with meals containing fat); consider monitoring trough 25-OH D more frequently

— Severe hepatic failure may need calcifediol (25-OH D3) if available, bypassing hepatic step

Step 3 management: For a 78-year-old in assisted living with two falls in 6 months, your order set includes 25-OH D level, vitamin D3 800–1000 IU/day if deficient, calcium intake assessment, medication deprescribing, PT referral for balance/strength, and home safety evaluation — not a single intervention.

Elderly (≥65):

Chronic kidney disease:

Hepatic impairment:

Nephrotic syndrome: urinary loss of vitamin D-binding protein → low total 25-OH D; supplement and treat underlying disease

Special Populations — Pregnancy, Pediatrics, and Other Subgroups

— Routine universal screening not recommended by ACOG or USPSTF

— Screen if risk factors: dark skin, veiling, limited sun, vegan, obesity, malabsorption

— RDA in pregnancy/lactation: 600 IU/day (most prenatal vitamins provide 400–600 IU)

— Deficiency treated with 1000–2000 IU/day; up to 4000 IU/day considered safe upper limit

— Severe maternal deficiency → neonatal hypocalcemia, congenital rickets, enamel defects

— Avoid mega-bolus dosing in pregnancy

— AAP: all breastfed and partially breastfed infants → 400 IU/day vitamin D from the first few days of life until taking ≥1 L/day vitamin D–fortified formula or milk

— Formula-fed infants taking <1 L/day also need supplementation

— Maternal high-dose D (6400 IU/day) can enrich breast milk as alternative — less standard

— RDA 600 IU/day from age 1 onward

— Risk groups: obesity, dark skin, anticonvulsants, malabsorption, exclusive breastfeeding without supplementation

— Treat deficiency: 2000 IU/day × 6 weeks (1–18 y) or 50,000 IU/week × 6 weeks, then maintenance

— Roux-en-Y and BPD/DS — lifelong fat-soluble vitamin monitoring

— Typical dose: D3 3000 IU/day or 50,000 IU weekly, titrated

— Monitor q6 months initially, then annually

— Higher rates of deficiency; counsel without stigmatization; offer routine supplementation in at-risk patients

Board pearl: The classic infant vignette — exclusively breastfed, dark-skinned, presenting with hypocalcemic seizures or rickets findings — is vitamin D deficiency from inadequate supplementation, and the AAP answer is 400 IU/day starting in the first days of life.

Pregnancy:

Infants and breastfeeding:

Children/adolescents:

Adolescents with anorexia nervosa: universal screening for vit D and bone health; supplement plus refeeding

Patients post-bariatric surgery:

Dark-skinned and veiled populations:

Athletes/military: high prevalence of insufficiency in indoor athletes; supplement to optimize performance and stress-fracture prevention

Complications and Adverse Outcomes

— Osteomalacia — defective mineralization, bone pain, pseudofractures, proximal myopathy

— Rickets — pediatric growth plate disease, bowing, growth retardation, dental defects

— Osteoporosis — accelerated bone loss via secondary hyperPTH; fragility fractures

— Fragility fractures — hip, vertebral, distal radius

— Hypocalcemia → paresthesias, tetany, Chvostek/Trousseau signs, QT prolongation, seizures (especially infants)

— Secondary hyperparathyroidism → cortical bone resorption, subperiosteal erosions

— Hypophosphatemia → muscle weakness, rhabdomyolysis (rare), respiratory muscle weakness

— Falls — proximal myopathy, postural instability

— Sarcopenia worsening

— Frailty progression

— Permanent skeletal deformity if untreated rickets (genu varum/valgum)

— Dental enamel hypoplasia, increased caries

— Growth retardation, delayed milestones

— Hypercalcemia — fatigue, confusion, polyuria, constipation, AKI

— Hypercalciuria — nephrolithiasis, nephrocalcinosis

— Vitamin D toxicity at 25-OH D >100–150 ng/mL

— Increased falls with annual mega-bolus dosing in elders

— Increased all-cause mortality observed in deficiency; supplementation has not consistently reduced mortality, CV events, or cancer in RCTs (VITAL trial)

— Resist boards bait that says "give vit D to prevent cancer/CVD" — not supported

— Severe deficiency associated with preeclampsia, gestational diabetes (associations, not proven causations)

— Neonatal hypocalcemia and congenital rickets in extreme maternal deficiency

Key distinction: Osteoporosis = low bone mass with normal mineralization; Osteomalacia = normal-ish bone mass with defective mineralization. Both can coexist; both can cause fractures. Vitamin D deficiency aggravates both — treat the deficiency first, then assess for osteoporosis-specific therapy.

Skeletal complications:

Calcium/phosphate disturbance complications:

Functional complications:

Pediatric long-term:

Complications of treatment (over-supplementation):

Associations (do not present as treatment indications on boards):

Pregnancy-related:

When to Escalate Care — Consult and Inpatient Triage

— Asymptomatic or mildly symptomatic deficiency

— No severe hypocalcemia

— No major end-organ effects

— Refractory deficiency despite documented adherence and adequate dosing

— Suspected hereditary rickets (VDR mutation, 1α-hydroxylase deficiency)

— Coexisting primary hyperparathyroidism or atypical PTH dynamics

— Granulomatous disease with dysregulated calcium

— Pediatric rickets requiring specialty management

— CKD stage 4–5 with secondary hyperPTH

— Need for active vitamin D analogs

— Nephrolithiasis with hypercalciuria

— Suspected Fanconi syndrome, tumor-induced osteomalacia

— Suspected celiac, IBD, pancreatic insufficiency, post-bariatric malabsorption requiring evaluation

— Symptomatic hypocalcemia — tetany, seizures, laryngospasm, QT prolongation, arrhythmia

— Severe hypocalcemia (corrected Ca <7.5 mg/dL) even if minimally symptomatic

— Severe vitamin D toxicity with hypercalcemia >14 mg/dL, AKI, altered mental status

— Pediatric hypocalcemic seizures

— Order: IV access, IV calcium gluconate 1–2 g over 10 min, then infusion

— Continuous ECG monitoring (QT, arrhythmia)

— Replete magnesium first or concurrently if low

— Check ionized Ca q2–4h, PTH, 25-OH D, phosphate, Mg, creatinine

— Start oral calcium + active vit D (calcitriol) for sustained correction

— Identify and treat underlying cause

— Hypocalcemic seizures

— Severe deformity needing orthopedic involvement

— Suspected non-nutritional rickets needing genetic workup

CCS pearl: Don't forget to check magnesium and replete it first in any patient with refractory hypocalcemia — low Mg both impairs PTH secretion and creates end-organ PTH resistance, defeating calcium and vitamin D repletion until corrected.

Outpatient management is appropriate for most cases:

Refer to endocrinology when:

Refer to nephrology when:

Refer to GI when:

Inpatient admission criteria:

CCS workflow for symptomatic hypocalcemia:

Pediatric admission for rickets:

Key Differentials — Same-Category (Calcium/Bone) Causes

— ↑ Ca, ↓/normal phosphate, ↑ PTH, ↑ urine Ca

— Often asymptomatic, found on routine labs

— Sestamibi scan for adenoma localization

— Treatment: parathyroidectomy if criteria met (Ca >1 mg/dL above upper limit, eGFR <60, T-score ≤−2.5, age <50, urine Ca >400 mg/day, stones)

— ↓/normal Ca, ↑ phosphate, ↑ PTH, ↑ FGF23, low calcitriol

— Different from vit D deficiency: phosphate is high, not low

— ↓ Ca, ↑ phosphate, ↓ PTH

— Often post-thyroidectomy or autoimmune (APS-1)

— Treatment: calcium + calcitriol (active form, since PTH-driven activation is gone)

— ↓ Ca, ↑ phosphate, ↑ PTH (end-organ resistance)

— Albright hereditary osteodystrophy phenotype

— Normal Ca, phosphate, PTH, 25-OH D

— Low BMD on DEXA, fragility fracture history

— Markedly ↑ alk phos with normal Ca, phosphate, PTH, 25-OH D

— Focal bone pain, deformity, hearing loss

— Bone scan shows focal uptake; treatment is bisphosphonates

— Mixed picture in CKD — high-turnover (osteitis fibrosa) vs low-turnover (adynamic bone)

— Bone biopsy may be needed; managed per KDIGO

— Children with bowing, normal Ca, low phosphate, normal 25-OH D, inappropriately normal/low 1,25-(OH)2 D, ↑ FGF23

— Treatment: phosphate + calcitriol or burosumab

Key distinction: Use the calcium + phosphate + PTH triad as your matrix. Vit D deficiency = low/normal Ca, low phosphate, high PTH. Primary hyperPTH = high Ca, low phosphate, high PTH. Hypoparathyroidism = low Ca, high phosphate, low PTH. Memorize this 3×3 — it solves most of the bone/Ca section.

Primary hyperparathyroidism:

Secondary hyperparathyroidism from CKD:

Hypoparathyroidism:

Pseudohypoparathyroidism:

Osteoporosis (without deficiency):

Paget disease of bone:

Renal osteodystrophy:

X-linked hypophosphatemic rickets:

Key Differentials — Other-Category Causes of Bone Pain/Weakness

— Diffuse musculoskeletal pain, tender points, fatigue, non-restorative sleep

— Normal labs (Ca, PTH, 25-OH D, ESR, CRP)

— Treat with exercise, CBT, duloxetine, milnacipran, pregabalin

— Age >50, shoulder/hip girdle stiffness >45 min morning, ↑ ESR/CRP

— Dramatic response to prednisone 15–20 mg/day

— Screen for concurrent giant cell arteritis

— Proximal weakness, ↑ CK, ↑ aldolase, EMG/biopsy abnormalities

— Skin findings (Gottron, heliotrope) in DM

— Treatment: glucocorticoids, immunosuppressants

— Proximal myopathy, fatigue, weight gain, ↑ TSH

— Treat with levothyroxine

— Proximal weakness, ± ↑ CK

— Stop statin, consider rechallenge or alternative

— Bone pain, anemia, hypercalcemia, renal dysfunction, M-spike on SPEP

— Lytic lesions on imaging (no uptake on bone scan, low alk phos)

— Workup: SPEP/UPEP, free light chains, skeletal survey or whole-body MRI

— Breast, prostate, lung, kidney, thyroid primaries

— Imaging shows lytic or blastic lesions

— Treatment depends on primary; bone-modifying agents (bisphosphonate/denosumab)

— Hip pain, glucocorticoid/alcohol use, sickle cell

— MRI sensitive; X-ray late finding

— Athletes, recent activity change; focal pain reproducible on percussion; MRI is best

— Can mimic vague musculoskeletal complaints; screen with PHQ-9

Board pearl: Proximal weakness + normal CK + diffuse bone pain + low phosphate → vitamin D deficiency/osteomalacia. Proximal weakness + high CK → inflammatory myopathy. Proximal stiffness (morning) + high ESR + age >50 → PMR. Anchor differential on the trio: weakness pattern, CK, inflammatory markers.

Fibromyalgia:

Polymyalgia rheumatica (PMR):

Inflammatory myopathies (polymyositis, dermatomyositis):

Hypothyroidism:

Statin-induced myopathy:

Multiple myeloma:

Metastatic bone disease:

Osteonecrosis (avascular necrosis):

Stress fracture:

Depression with somatic symptoms:

Secondary Prevention and Long-Term Plan

— Transition to maintenance dosing:

— Adults 19–70: 600–1000 IU/day

— Adults >70: 800–2000 IU/day

— Obese, malabsorption, anticonvulsant users: 2000–4000 IU/day or 50,000 IU monthly/weekly

— Pair with dietary calcium 1000–1200 mg/day (food preferred over supplements)

— Reassess 25-OH D annually in high-risk patients

— Food sources: fatty fish (salmon, mackerel, sardines), egg yolks, fortified dairy, fortified plant milks, fortified cereals, cod liver oil, UV-treated mushrooms

— Safe sun: brief midday exposure 2–3×/week to arms/legs; do not advise tanning beds; balance with skin cancer risk

— Weight-bearing and resistance exercise — improves BMD and reduces falls

— DEXA screening per USPSTF (women ≥65, men ≥70, or earlier with risk factors like glucocorticoid use, prior fragility fracture, low BMI, smoking, alcohol)

— FRAX score to estimate 10-year fracture risk

— Bisphosphonate (alendronate first-line) if T-score ≤−2.5 or FRAX hip ≥3% / major ≥20%

— Denosumab, teriparatide, romosozumab for refractory or high-risk

— PT for balance/strength (Tai Chi, Otago program)

— Home safety eval (rugs, lighting, grab bars)

— Vision/hearing optimization

— Medication review — deprescribe sedatives, anticholinergics, BP meds causing orthostasis

— Footwear assessment

— Post-bariatric: lifelong supplementation + annual labs

— CKD: per KDIGO, with nephrology

— Chronic glucocorticoid: ACR bone health protocol — Ca, vit D, DEXA, bisphosphonate

Step 3 management: Don't stop at repletion — bundle vitamin D therapy with calcium, exercise prescription, fall risk assessment, DEXA, and treatment of underlying contributors. Step 3 rewards comprehensive longitudinal plans, not single-drug answers.

After successful repletion (25-OH D ≥30 ng/mL):

Lifestyle and dietary counseling:

Bone health bundle for high-risk patients:

Fall prevention bundle (elderly):

Disease-specific maintenance:

Follow-Up, Monitoring, and Counseling Cadence

— Recheck 25-OH D at 3 months after starting therapy

— Goal: ≥30 ng/mL (Endocrine Society) or ≥20 ng/mL (IOM)

— Concurrently recheck: Ca, phosphate, PTH, creatinine, alk phos

— If insufficient response, extend repletion course, evaluate adherence and malabsorption

— Annual 25-OH D in high-risk patients (CKD, post-bariatric, malabsorption, chronic glucocorticoid, dark-skinned/veiled, institutionalized)

— Low-risk healthy adults on routine maintenance: no recurring lab checks needed once stable

— Patients on high-dose (≥50,000 IU weekly long-term) or active analogs: check Ca and 25-OH D q3 months initially

— Screen 24-h urine Ca if recurrent stones or hypercalciuria suspected

— Repeat 1–2 years after treatment initiation for osteoporosis

— Stable patients on bisphosphonate: q2–3 years

— Drug holiday consideration after 5 years oral / 3 years IV bisphosphonate

— Take with fat-containing meal for absorption

— D3 preferred over D2 OTC

— Avoid stacking multiple supplements with vit D (multivitamin + dedicated supplement) — risk of unintended high dose

— Sunscreen does not need to be discontinued — diet/supplementation is safer than UV strategy

— Discuss false advertising — vit D does not prevent COVID, cancer, or CV events at evidence-grade A

— STEADI fall-risk screening in elders

— ACR glucocorticoid-induced osteoporosis bundle

— Bariatric postoperative vitamin protocols

— Pregnancy/breastfeeding pediatric supplementation counseling

CCS pearl: Set the 3-month follow-up appointment at the visit when you start repletion — advance the clock 12 weeks, then re-order 25-OH D + Ca + PTH. Step 3 grades you on closing the loop, not just initiating therapy.

Follow-up labs during repletion:

Maintenance follow-up:

Monitoring for toxicity:

DEXA cadence:

Patient counseling points:

Documentation/quality measures:

Ethical, Legal, and Patient Safety Considerations

— USPSTF I statement for asymptomatic adults — ordering 25-OH D as a routine wellness panel is low-value care and may not be reimbursed by some payers

— Choosing Wisely lists "don't routinely screen for vitamin D deficiency" in low-risk adults

— Documenting risk factors before ordering supports medical necessity

— Discuss limited evidence for non-skeletal benefits (cancer, CV, mood) — avoid making claims unsupported by evidence

— Patients on supplements purchased OTC often unaware of cumulative dose from multivitamin + dedicated vit D — explicitly review

— Avoid annual mega-bolus dosing in elders — Sanders trial showed increased fall and fracture rate

— Confirm dosing units (IU vs mcg: 1 mcg = 40 IU) — pharmacy/OTC labeling confusion causes dosing errors

— Reconcile supplements at every visit; ask about herbals and online purchases

— Severe rickets in an infant/child may raise concern for neglect (failure to supplement, failure to seek care) — clinician must distinguish nutritional deficiency from medical neglect and report when criteria met under state law

— Engage social work and pediatrics before reporting; document attempts at education and barriers

— Religious/cultural objections to supplementation do not exempt mandatory reporting when child's health is endangered

— Post-bariatric patients lost to follow-up develop refractory deficiency, osteomalacia, and fractures — institute structured handoff to primary care with lifelong supplementation written into discharge summary

— Hospital discharge after hip fracture: ensure vit D + calcium + bone-modifying agent + outpatient follow-up arranged; this is a National Patient Safety/quality metric

— Higher prevalence in dark-skinned, veiled, low-income populations — ensure access to affordable OTC D3 and dietary counseling without judgment

Step 3 management: A 4-month-old with hypocalcemic seizures from exclusive breastfeeding without vit D supplementation requires treatment first, parental education, and a careful determination of whether reporting to CPS is warranted — most cases are remedied with education and follow-up, not punitive reporting.

Avoid over-screening (low-value care):

Informed consent and shared decision-making:

Patient safety — preventing harm:

Pediatric mandatory reporting consideration:

Transition-of-care risk:

Equity considerations:

High-Yield Associations and Rapid-Fire Clinical Facts

— Deficiency <20 ng/mL, insufficiency 20–29, sufficiency ≥30, toxicity >100

— RDA: 600 IU (19–70 y), 800 IU (>70 y), 400 IU (infants)

— Tolerable upper intake: 4000 IU/day adults, 1000–3000 IU/day children (age-dependent)

— Repletion: D3 50,000 IU weekly × 8 weeks

— Recheck at 3 months

— 1 mcg = 40 IU

— Deficiency: ↓ 25-OH D, ↓/normal Ca, ↓ phosphate, ↑ PTH, ↑ alk phos

— Primary hyperPTH: ↑ Ca, ↓ phosphate, ↑ PTH

— Hypoparathyroidism: ↓ Ca, ↑ phosphate, ↓ PTH

— Paget: isolated ↑ alk phos

— Looser zones (pseudofractures) → osteomalacia

— Rachitic rosary, frayed metaphyses → pediatric rickets

— Subperiosteal resorption, salt-and-pepper skull → hyperPTH

— Lytic lesions, "rain-drop" skull → multiple myeloma

— Phenytoin + vit D deficiency

— Glucocorticoids + osteoporosis (ACR bundle)

— Thiazide + vit D = hypercalcemia risk

— Cinacalcet for severe secondary hyperPTH in dialysis

— Calcitriol (active) for hypoparathyroidism, CKD, 1α-hydroxylase deficiency

— Infants: 400 IU/day from birth if breastfed

— Post-bariatric: lifelong supplementation

— Sarcoidosis: cautious vit D, target lower 25-OH D

— Pregnancy: 600 IU/day, screen only if risk factors

— VITAL trial — vit D ± omega-3 did NOT reduce cancer/CV events in primary prevention

— Sanders 2010 — annual 500,000 IU bolus → ↑ falls/fractures

— USPSTF I statement — insufficient evidence to screen asymptomatic adults

— AAP — 400 IU/day for all breastfed infants

— KDIGO — CKD-MBD management

— "Give vit D to prevent cancer" — no

— "Give vit D to prevent CV disease" — no

— "Routinely screen all adults" — no

Board pearl: When in doubt about whether to supplement, ask: Is this patient at risk for deficiency, or do they already have it? If yes to either → supplement. If healthy, asymptomatic, low-risk → diet and counseling only.

Numerical anchors:

Classic biochem:

Imaging buzzwords:

Drug pearls:

Special populations quick-fire:

Trials/guidelines to know:

Don't fall for:

Board Question Stem Patterns

— 78-year-old woman, two falls, lives alone, on furosemide and lorazepam, 25-OH D 14 ng/mL

— Best next step: D3 50,000 IU weekly × 8 weeks + calcium 1200 mg/day from diet + PT for balance + deprescribe lorazepam + home safety eval

— Wrong: annual 500,000 IU bolus (harm); calcitriol (not indicated)

— 42-year-old wants "vitamin D screening" at annual visit, no risk factors

— Best next step: Do not order 25-OH D; counsel on diet, exercise, sun exposure

— Wrong: order 25-OH D as routine screening

— 5-month-old, exclusively breastfed, dark-skinned, presents with seizure; Ca 6.8, phosphate low, alk phos high, 25-OH D <10

— Diagnosis: vitamin D deficiency/rickets with hypocalcemic seizure

— Treatment: IV calcium gluconate acutely + start vitamin D3 + ongoing 400 IU/day

— Counseling: all breastfed infants should receive 400 IU/day from first days

— 38-year-old, 3 years post-Roux-en-Y, bone pain, low 25-OH D, low Ca, high PTH, high alk phos

— Treatment: high-dose D3 50,000 IU weekly indefinitely + calcium citrate + B12 + iron + annual labs

— 45-year-old man with cough, hilar adenopathy, Ca 11.8, PTH suppressed, 25-OH D normal, 1,25-(OH)2 D elevated

— Treatment: IV saline + prednisone; avoid vit D/Ca supplements

— Wrong: start vit D supplementation

— 55-year-old on prednisone for vasculitis × 6 months, low 25-OH D

— Bundle: calcium 1000–1200 mg + vit D 800–2000 IU + DEXA + bisphosphonate if moderate–high FRAX

— eGFR 22, PTH 380, Ca 8.5, phosphate 5.5, 25-OH D 18

— Stepwise: repletion D3 first → if PTH persists, add active analog (calcitriol/paricalcitol) + phosphate binder; nephrology comanagement

Key distinction: Read the stem for risk factors before ordering screening — Step 3 rewards risk-stratified ordering, not reflexive testing.

Stem 1 — Elderly faller:

Stem 2 — Healthy asymptomatic adult:

Stem 3 — Breastfed infant:

Stem 4 — Post-bariatric:

Stem 5 — Sarcoidosis with hypercalcemia:

Stem 6 — Chronic glucocorticoid:

Stem 7 — CKD stage 4:

One-Line Recap

Vitamin D deficiency is screened only in at-risk patients (elderly fallers, malabsorption, post-bariatric, chronic glucocorticoids, CKD, dark-skinned/veiled, exclusively breastfed infants), diagnosed by serum 25-OH D <20 ng/mL with supportive biochemistry (low/normal Ca, low phosphate, high PTH, high alk phos), and treated with cholecalciferol (D3) 50,000 IU weekly × 8 weeks then 800–2000 IU/day maintenance, bundled with calcium, fall prevention, and management of underlying contributors — while avoiding both indiscriminate screening of healthy adults and harmful mega-bolus dosing.

Step 3 management: The exam-winning answer is rarely "just give vitamin D" — it is the comprehensive, risk-stratified, follow-up-anchored plan that integrates pharmacology, lifestyle, fall prevention, bone health screening, and patient safety considerations into one coherent strategy that you can defend on rounds, in clinic, and on the CCS interface.

Numbers to lock: Deficiency <20, sufficient ≥30, RDA 600 (19–70) / 800 (>70), infants 400 IU/day from birth, repletion 50,000 IU weekly × 8 weeks, recheck at 3 months.

Biochem matrix: Vit D deficiency = ↓ Ca, ↓ phosphate, ↑ PTH, ↑ alk phos — distinct from primary hyperPTH (↑ Ca, ↓ phosphate, ↑ PTH) and hypoparathyroidism (↓ Ca, ↑ phosphate, ↓ PTH).

Don't do: routine screening of asymptomatic low-risk adults (USPSTF I); annual mega-bolus dosing in elders (↑ falls); supplementation in active granulomatous hypercalcemia (use steroids + saline instead); claim cancer/CV prevention (VITAL negative).

Bundle: Always pair vit D repletion with calcium intake assessment, fall prevention in elders, DEXA when indicated, deprescribing of culprit drugs, and a scheduled 3-month follow-up lab — Step 3 rewards the longitudinal plan, not the isolated prescription.