Osteomalacia and Rickets

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Lecture topics

The same defect has two age-dependent expressions
Vitamin D-binding protein carries the precursor
Renal TRPV5 supports calcium retention
Inherited defects disrupt different steps
Cartilage remnants extend into the marrow space
Bowing of the legs follows weight bearing
Renal osteodystrophy is broader than osteomalacia
Core textbook references

Slide index & full transcript (73 slides)

Text from the original slides, in presentation order. Diagrams and images remain in the viewer above.

Slide 1 · Osteomalacia and Rickets

Impaired mineralization of bone matrix

Bone development • matrix mineralization • skeletal fragility

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Distinguish undermineralized bone from reduced bone mass.

Explain vitamin D metabolism and calcium–phosphate feedback.

Relate growth-plate abnormalities to the deformities of rickets.

Recognize adult osteomalacia and its skeletal consequences.

Integrate etiologies, morphology, and laboratory reasoning.

Slide 3 · The same defect has two age-dependent expressions

Rickets — growing skeleton

Osteomalacia — mature skeleton

Unmineralized matrix at the growth plate.

Abnormal endochondral ossification.

Distortion of developing bones under load.

New remodeling osteoid mineralizes poorly.

Growth plates are closed.

Fractures and microfractures of weakened bone.

The defining lesion is defective mineralization, not deficient osteoid production.

Slide 4 · Mineralization requires a matrix and a mineral supply

An osteoblast-produced organic scaffold becomes mechanically competent when mineral is deposited.

Osteoblast creates osteoid

Calcium + phosphate available

Mineral deposits in matrix

Stiff, load-bearing bone

Insufficient calcium or phosphate disrupts the deposition step.

Matrix may be present in excess but remain unmineralized.

Consequences depend on whether the bone is growing or remodeling.

Slide 5 · Growth plate versus adult remodeling

Endochondral growth

Remodeling in adult bone

Cartilage expands at the epiphyseal plate.

Cartilage becomes provisionally calcified.

Bone replaces cartilage at the metaphysis.

Old bone is removed and replaced.

Osteoblasts lay down fresh osteoid.

The new osteoid subsequently mineralizes.

A mineralization block affects growth-plate architecture only before plate closure.

Slide 6 · Osteomalacia is not synonymous with osteoporosis

Osteomalacia

Osteoporosis

Mineralization of newly formed bone is impaired.

An excess of unmineralized osteoid persists.

Reduced mechanical strength predisposes to fracture.

Amount of bone tissue is reduced.

Remaining bone has normal mineralization.

Fracture risk rises through loss of bone mass.

The disorders may coexist, but they are not mechanistically interchangeable.

Slide 7 · The developmental window determines the phenotype

Bone growth and bone remodeling both require mineral, but they use it in different anatomic settings.

Open growth plates

Deficient mineral deposition

Disordered growth architecture

Rickets and deformity

Epiphyseal cartilage continues to proliferate.

Insufficient provisional calcification impairs orderly replacement.

Mechanical loads deform the structurally weak skeleton.

In a skeletally mature adult, the corresponding lesion is osteomalacia.

Slide 8 · Rickets and osteomalacia: Anatomic comparison

Feature

Rickets

Osteomalacia

Skeletal maturity

Growth plates open

Growth plates closed

Primary setting

Growth-plate ossification

Bone remodeling

Matrix finding

Excess unmineralized osteoid

Persistent, thick osteoid seams

Architecture

Distorted costochondral / metaphyseal regions

Overall contour may remain normal

Mechanical result

Developmental bowing and deformity

Microfractures and overt fractures

Slide 9 · Calcium and phosphate are both required

The mineral phase depends on adequate calcium and phosphate availability.

Deficiency of either limits effective mineral deposition in osteoid.

Vitamin D and parathyroid hormone coordinate mineral homeostasis.

Defective phosphate handling can impair bone even when serum calcium recovers.

A normal calcium result does not prove that skeletal mineralization is normal.

Slide 10 · Vitamin D metabolism links skin, liver, and kidney

Skin / diet

Vitamin D input

Liver

25-hydroxylation

Kidney

1α-hydroxylation

Target tissues

Calcium–phosphate balance

25(OH)D is the major circulating metabolite; 1,25(OH)₂D is the active hormone.

PTH ↑ kidney activation | FGF23 ↓ kidney activation

Slide 11 · UVB-dependent vitamin D production

Skin 7-dehydrocholesterol undergoes a photochemical conversion.

UVB exposure produces cholecalciferol (vitamin D₃).

Reduced UVB exposure can limit endogenous vitamin D supply.

Melanin absorbs UV light and can reduce production under similar exposure conditions.

The ultraviolet-to-vitamin D step is upstream of liver and kidney activation.

Slide 12 · Dietary vitamin D requires intestinal absorption

Diet and supplements can provide vitamin D independently of skin synthesis.

Dietary uptake depends on absorption of fat-soluble compounds.

Malabsorption can reduce effective vitamin D entry despite oral intake.

A low dietary supply amplifies the effect of limited sunlight exposure.

The nutritional pathway and cutaneous pathway converge in the bloodstream.

Slide 13 · Vitamin D-binding protein carries the precursor

Vitamin D derived from skin and food joins the same transport pathway.

Skin or gut source

Vitamin D enters blood

Vitamin D binds DBP

Delivery to the liver

Vitamin D circulates bound to vitamin D-binding protein (DBP).

Transport is followed by biochemical activation in two organs.

Source of entry does not change the subsequent hepatic step.

Slide 14 · Hepatic 25-hydroxylation creates 25(OH)D

The liver converts vitamin D into its major circulating 25-hydroxy metabolite.

Vitamin D₃ delivered

Hepatic 25-hydroxylases

25-hydroxyvitamin D

Renal substrate

CYP family hydroxylases participate in the first activation step.

25(OH)D is the circulating species discussed in deficiency testing.

Substrate supply can be low even when kidney enzymes are intact.

Slide 15 · Renal 1α-hydroxylation produces the active hormone

The kidney converts 25(OH)D to 1,25-dihydroxyvitamin D.

Circulating 25(OH)D

Renal 1α-hydroxylase

1,25(OH)₂D

VDR-mediated action

The renal enzyme is under endocrine and mineral-feedback control.

Kidney disorders can reduce the final activation step.

A normal precursor supply alone cannot guarantee sufficient active hormone.

Slide 16 · The four controls of renal 1α-hydroxylase

Signals increasing activity

Signals decreasing activity

Hypocalcemia induces PTH secretion.

PTH enhances renal 1α-hydroxylase.

Hypophosphatemia upregulates enzyme expression.

1,25(OH)₂D restrains its own synthesis.

FGF23 inhibits enzyme expression.

The balance depends on mineral status.

Feedback coordinates hormone activation with calcium–phosphate availability.

Slide 17 · Calcium decline triggers a compensatory PTH response

The body prioritizes maintenance of extracellular ionized calcium.

Calcium falls

Parathyroid PTH rises

Renal + skeletal response

Calcium partially restored

PTH enhances renal activation of vitamin D.

PTH promotes bone resorption indirectly through osteoblast RANKL.

PTH decreases renal calcium loss but increases phosphate loss.

Slide 18 · Hypophosphatemia also activates renal vitamin D synthesis

Low phosphate is itself an input to renal 1α-hydroxylase regulation.

Serum phosphate low

1α-hydroxylase increases

Active vitamin D rises

Intestinal mineral uptake supported

This is a compensatory response to reduced phosphate availability.

Concurrent PTH-mediated phosphaturia can perpetuate depletion.

The final mineralization outcome depends on actual mineral supply.

Slide 19 · FGF23: Endocrine brake on active vitamin D

Bone-derived signal

Kidney-directed effects

Osteocytes and osteoblasts produce FGF23.

FGF23 participates in phosphate regulation.

Pathologic excess may be hereditary or tumor-associated.

FGF23 suppresses renal 1α-hydroxylase.

Phosphate excretion increases through renal mechanisms.

Reduced phosphate supply may produce rickets or osteomalacia.

FGF23 excess provides a non-nutritional route to defective mineralization.

Slide 20 · Active vitamin D regulates its own formation

1,25(OH)₂D is the active hormonal form of vitamin D.

Increasing active hormone inhibits expression of renal 1α-hydroxylase.

Feedback constrains further active-hormone formation.

It is one of several simultaneous inputs to renal enzyme activity.

The vitamin D pathway is regulated—not simply a one-way conversion chain.

Slide 21 · The VDR–RXR complex regulates target genes

Active vitamin D acts through a nuclear receptor transcriptional mechanism.

1,25(OH)₂D binds VDR

VDR associates with RXR

Complex binds DNA response elements

Target transcription changes

The vitamin D receptor is widely distributed among tissues.

Intestinal, renal, and skeletal target genes alter mineral handling.

These effects connect endocrine signaling to bone mineralization.

Slide 22 · Intestinal TRPV6 supports calcium absorption

Vitamin D signaling strengthens intestinal calcium transport.

Active vitamin D

VDR–RXR activation

TRPV6 transcription

Duodenal calcium uptake

TRPV6 encodes a calcium transport channel.

Reduced active vitamin D can impair calcium absorption.

The skeletal effect is partly mediated by reduced mineral availability.

Slide 23 · Renal TRPV5 supports calcium retention

Vitamin D and PTH modify calcium reabsorption in the distal nephron.

Active vitamin D / PTH

TRPV5 expression

Renal calcium influx

Less calcium lost

TRPV5 mediates calcium entry in distal tubular cells.

Both vitamin D and PTH participate in its regulation.

Calcium conservation helps defend plasma calcium during deficiency.

Slide 24 · RANKL links hormone signals to bone resorption

Bone-resorbing osteoclasts respond indirectly to osteoblast signals.

Vitamin D / PTH signaling

Osteoblast RANKL ↑

Preosteoclast RANK activated

Osteoclast maturation

Osteoclasts resorb mineralized bone and release calcium and phosphate.

This can support serum calcium during inadequate intestinal uptake.

Chronic compensation may consume existing bone reserves.

Slide 25 · Osteocalcin links osteoblast activity to mineralization

Vitamin D signaling also influences the bone-forming compartment.

Active vitamin D

Osteoblast response

Osteocalcin synthesis

Mineral deposition supported

Osteoid is first synthesized as an organic matrix.

Osteocalcin is a calcium-binding protein involved in bone deposition.

Deficient substrate availability can still limit final mineralization.

Slide 26 · Calcium homeostasis can mask phosphate depletion

What is being defended?

What may remain abnormal?

Ionized extracellular calcium is tightly regulated.

PTH increases calcium conservation and skeletal release.

Plasma calcium can return toward normal.

PTH enhances phosphate excretion.

Hypophosphatemia can persist despite calcium recovery.

New osteoid may then mineralize inadequately.

Assess the full feedback sequence rather than interpreting calcium in isolation.

Slide 27 · Causes converge on insufficient mineralization

Upstream defect

Why mineralization fails

Low vitamin D supply

Lower delivery of vitamin D precursor

Inadequate dietary calcium

Reduced mineral substrate

Intestinal malabsorption

Impaired absorption of fat-soluble vitamin D

Renal disease

Less active 1,25(OH)₂D synthesis

Phosphate depletion / wasting

Insufficient phosphate for matrix mineralization

Inherited pathway defects

Vitamin D response or mineral handling altered

Slide 28 · Low sunlight exposure restricts endogenous supply

Less cutaneous UVB exposure means less cholecalciferol generation.

Northern latitudes and extensive skin covering as contexts.

The same mechanism can occur at low or high latitudes.

Clinical susceptibility depends on diet and other patient factors.

Slide 29 · Nutritional deficiency reduces the available substrate

Dietary insufficiency of vitamin D or calcium can impair mineralization.

Vitamin D availability and calcium availability are related but distinct.

A diet may fail to compensate for limited cutaneous vitamin D synthesis.

The downstream lesion is mineralization failure, not absent matrix production.

Slide 30 · Fat malabsorption interrupts the nutritional pathway

Vitamin D is fat-soluble: Intestinal absorption is an upstream checkpoint.

Fat malabsorption

Vitamin D uptake reduced

Active hormone availability falls

Mineral absorption falls

The defect begins before liver and renal hydroxylation.

Available vitamin D substrate may become inadequate.

The mechanism is relevant to secondary osteomalacia.

Slide 31 · Renal disease alters both vitamin D and phosphate

Chronic kidney dysfunction can produce overlapping mineral and bone lesions.

Renal dysfunction

Active vitamin D synthesis ↓

Intestinal calcium absorption ↓

Matrix mineralization affected

Renal disease can induce secondary hyperparathyroidism.

Phosphate excretion and systemic acid–base balance may also be altered.

Renal osteodystrophy encompasses more than osteomalacia alone.

Slide 32 · Phosphate depletion can be sufficient to impair bone

Phosphate is required alongside calcium for skeletal mineral deposition.

Excessive renal phosphate loss can lower available phosphate.

PTH-driven phosphaturia aggravates deficiency-associated mineralization failure.

An FGF23-mediated disorder offers another route to phosphate depletion.

Slide 33 · Inherited defects disrupt different steps

Vitamin D pathway

Phosphate pathway

Inherited defects may impair vitamin D metabolism.

Some variants disrupt vitamin D receptor function.

Target tissues fail to respond normally to active hormone.

Inherited abnormalities can cause excessive FGF23 activity.

Renal phosphate loss limits available substrate.

Affected children may develop hypophosphatemic rickets.

Inherited rickets is not invariably caused by dietary deficiency.

Slide 34 · Excess FGF23 creates hypophosphatemic disease

Overactive bone-to-kidney signaling diverts mineral physiology away from deposition.

FGF23 inappropriately high

Renal phosphate loss

Phosphate depletion

Rickets / osteomalacia

The textbook recognizes inherited and tumor-associated forms.

FGF23 also suppresses renal activation of vitamin D.

These effects reinforce inadequate mineral deposition.

Slide 35 · Tumor-associated phosphate wasting is a distinct mechanism

Certain tumors are associated with inappropriately high FGF23 production.

Phosphate loss can lead to osteomalacia in adults.

The endocrine mechanism differs from limited UVB or dietary vitamin D.

A careful etiologic evaluation distinguishes nutrient deficiency from phosphate wasting.

Slide 36 · Vitamin D deficiency starts an endocrine cascade

Inadequate vitamin D availability reduces mineral uptake from the gut.

Vitamin D supply ↓

Active hormone effect ↓

Calcium / phosphate uptake ↓

PTH compensation triggered

Calcium falls initially in the causal model.

The parathyroid response is a homeostatic consequence.

Phosphate can remain inadequate for mineralization.

Slide 37 · PTH compensation preserves calcium at a skeletal cost

Secondary hyperparathyroidism is a response to calcium stress.

Calcium ↓

PTH ↑

Bone resorption / renal retention

Calcium normalizes toward baseline

PTH increases renal calcium conservation.

RANKL-mediated bone resorption releases stored calcium.

The concurrent phosphate loss creates a competing problem.

Slide 38 · Phosphaturia explains persistent undermineralization

Defending calcium concentration does not assure adequate phosphate concentration.

PTH secretion ↑

Urinary phosphate excretion ↑

Available phosphate ↓

Osteoid stays unmineralized

Hypophosphatemia may persist despite near-normal calcium.

Excess unmineralized matrix accumulates where bone is newly formed.

The final phenotype reflects skeletal maturity.

This is the mechanistic link between endocrine compensation and osteoid accumulation.

Slide 39 · Why serum calcium may be misleading

Compensated state

Uncompensated skeletal effect

Calcium is mobilized from bone.

Renal calcium excretion decreases.

The measured circulating calcium may be near normal.

Phosphate continues to be lost in urine.

Cartilage/osteoid mineralization remains defective.

Weak bone and growth-plate abnormalities continue.

Slide 40 · Normal endochondral ossification has an ordered sequence

Growth plate cartilage is a temporary scaffold for newly formed long bone.

Chondrocytes proliferate

Hypertrophic zone matures

Cartilage calcifies

Bone replaces cartilage

Cell arrangement is ordered in longitudinal columns.

Provisional cartilage mineralization precedes replacement by bone.

Loss of this sequence is fundamental to rickets.

Slide 41 · Architecture of a normal and rachitic growth plate

Original schematic — not a histology image

Resting cartilage

Proliferative columns

Hypertrophic cartilage

Mineralization / bone

Resting cartilage

Proliferative columns

Hypertrophic cartilage

Mineralization / bone

Expanded irregular zone

Orderly growth plate

Rachitic growth plate

Slide 42 · Rickets begins with failed provisional calcification

Epiphyseal cartilage continues growing but fails to calcify normally.

Chondrocytes fail to complete orderly maturation and disintegration.

The growth-plate region expands instead of transitioning cleanly to bone.

This initiates the histologic disorganization of rickets.

Slide 43 · Cartilage remnants extend into the marrow space

Irregular masses of incompletely removed cartilage persist.

These remnants can project into the adjacent marrow cavity.

They mark failure of orderly cartilage-to-bone replacement.

The abnormal substrate distorts developing metaphyseal architecture.

Slide 44 · Osteoid is deposited on an inadequate scaffold

Osteoblast deposition continues despite defective mineralization of cartilage remnants.

Cartilage persists

Osteoid coats remnants

Mineralization remains incomplete

Weak trabecular structure

The lesion combines abnormal residual cartilage and unmineralized osteoid.

Bone production is not the same as production of mineralized bone.

Accumulated poorly mineralized matrix contributes to deformation.

Slide 45 · The osteochondral junction expands laterally

Architectural disorganization becomes a macroscopic metaphyseal abnormality.

Disordered cartilage maturation

Abnormal osteoid deposition

Growth zone widens

Osteochondral junction enlarges

Normal cartilage palisades are lost.

Irregular osteochondral boundaries replace an organized junction.

Gross widening reflects accumulated poorly mineralized tissue.

Slide 46 · Microfracture repair adds fibrovascular tissue

Weak mineralized tissue develops microfractures under mechanical stress.

Capillaries and fibroblasts proliferate in disorganized zones.

This reparative response further disturbs growth-plate architecture.

The pathologic process is mechanical plus metabolic—not purely inflammatory.

Slide 47 · The developing skeleton deforms under mechanical loads

The distribution of deformity changes as an affected child grows.

Weak mineralization

Loading of compliant bones

Structural bending

Persistent skeletal deformity

Infants load the skull and chest disproportionately.

Walking transfers major load to pelvis, spine, and lower limbs.

Rickets expresses the interaction of tissue weakness and mechanical stress.

Slide 48 · Age changes the sites of visible rickets

Before walking

After walking

Head and chest experience important compressive forces.

Occipital and parietal bone changes may be evident.

Costochondral junctions may become prominent.

Lower limbs bear greater longitudinal load.

Tibial bowing may develop.

Spinal and pelvic deformities become more conspicuous.

Slide 49 · Craniotabes reflects a softened infant skull

Softened occipital bone may flatten under pressure.

Parietal regions can be depressed by external force.

Elastic recoil allows the buckled bone to snap back.

This physical sign reflects reduced skeletal rigidity.

Slide 50 · Frontal bossing reflects accumulation of osteoid

Excess poorly mineralized osteoid accumulates during skull growth.

Frontal prominence can produce a squared head contour.

The change is a gross expression of altered mineralization during development.

Extent varies with disease severity and duration.

Slide 51 · The rachitic rosary marks widened costochondral junctions

Cartilage/osteoid accumulates at rib costochondral junctions.

The junctions become enlarged and visibly prominent.

Serial prominences along the chest wall constitute the rachitic rosary.

The morphology follows directly from abnormal growth-plate mineralization.

Slide 52 · Pigeon breast arises from rib and chest-wall deformation

Poorly mineralized ribs are more susceptible to respiratory-muscle forces.

Weak metaphyseal rib regions can bend inward.

The sternum may consequently protrude anteriorly.

The resulting pattern is described as pigeon breast deformity.

Slide 53 · Bowing of the legs follows weight bearing

Tibial bone is exposed to substantial mechanical load after ambulation begins.

Insufficient mineralization decreases resistance to bending.

Progressive deformation can produce bowed lower limbs.

The shape reflects both metabolic tissue weakness and habitual stress.

Slide 54 · Spinal and pelvic stress causes further deformity

Ambulation shifts load to axial and appendicular regions.

Spinal deformation may include lumbar lordosis.

The pelvis can be affected by the same mechanical weakness.

Severity depends on timing, duration, and anatomic stress.

Slide 55 · The visible lesions of childhood rickets

Each manifestation localizes mechanical stress onto poorly mineralized developing tissue.

Skull: Craniotabes

Compliant cranial bone buckles under pressure

Frontal bossing

Excess osteoid during skull growth

Rachitic rosary

Costochondral junction enlargement

Pigeon breast

Rib deformation with anterior sternal protrusion

Bowed tibiae

Weight-bearing load bends weak long bones

Lumbar lordosis

Axial skeletal deformation after ambulation

Slide 56 · Osteomalacia is a remodeling-stage mineralization defect

The adult skeleton has no open growth plates, but remodeling remains continuous.

Old bone resorbed

New osteoid deposited

Osteoid mineralization fails

Persistent undermineralized bone

Defective mineralization occurs in newly synthesized matrix.

Unmineralized osteoid is abnormally retained along trabeculae.

Overall skeletal contours need not change.

Slide 57 · Osteomalacia features widened unmineralized osteoid seams

Simplified trabecular cross-sections: Mineralized matrix versus unmineralized osteoid

Normally mineralized trabecula

Osteomalacic trabecula

Mineralized

Osteoid

Slide 58 · Histology: Osteoid persists around mineralized trabeculae

New osteoid is normally a transient stage before mineral deposition.

In osteomalacia, osteoid seams become abnormally prominent.

On H&E, unmineralized osteoid is pink around more basophilic mineralized trabeculae.

Assessment of a true specimen requires histologic context and appropriate tissue processing.

Slide 59 · The femoral neck is a site of skeletal fragility

Poorly mineralized remodeled bone has impaired mechanical competence.

Microfractures or overt fractures may affect femoral necks.

The problem is matrix quality, even without gross bony contour distortion.

Fracture risk follows the failure of new osteoid to mineralize.

Slide 60 · Vertebral bodies may develop microfractures

The axial skeleton undergoes continual loading and remodeling.

Under-mineralized trabecular tissue is susceptible to microfailure.

Vertebral bodies are specifically identified as vulnerable sites.

Repeated subclinical damage can precede a major fracture.

Slide 61 · Adult contour may be preserved despite weakness

Morphologic appearance

Mechanical consequence

Long-bone contour may remain essentially normal.

Trabeculae carry excessive unmineralized osteoid.

Gross inspection may not convey tissue quality.

Weakness predisposes to microfractures.

Femoral necks and vertebrae are vulnerable.

Fractures can occur without a rachitic shape change.

Slide 62 · Differential diagnosis: Defects of quantity or mineralization

Disorder

Primary abnormality

Characteristic setting

Osteomalacia

Failure to mineralize newly formed osteoid

Adult bone remodeling

Rickets

Failure to mineralize developing bone and growth plate

Skeletally immature patient

Osteoporosis

Reduced bone mass with normal mineralization

Adult skeletal fragility

Hyperparathyroid bone disease

PTH-driven osteoclast resorption

Primary or secondary PTH excess

Renal osteodystrophy

Mixed patterns of turnover and mineralization

Chronic kidney dysfunction

Slide 63 · Renal osteodystrophy is broader than osteomalacia

High-turnover processes

Low-turnover processes

Secondary hyperparathyroidism raises remodeling activity.

Resorption may predominate over formation.

Associated bone loss can coexist with mineral disturbance.

Adynamic bone has little cellular turnover.

Osteomalacia can be present in some low-turnover cases.

Mixed patterns also occur in renal disease.

Do not use “renal osteodystrophy” as a synonym for a single mineralization defect.

Slide 64 · Physiology guides etiologic investigation

Upstream defect

Why mineralization fails

Cutaneous vitamin D synthesis

UVB exposure and skin-related context

Dietary vitamin D / calcium

Intake and nutritional context

Intestinal absorption

Malabsorption and fat handling

Renal activation

Kidney function and vitamin D metabolism

Renal phosphate handling

Phosphate availability / wasting

Endocrine regulators

PTH–FGF23–vitamin D feedback

Slide 65 · 25(OH)D and 1,25(OH)₂D answer different questions

25(OH)D is generated in the liver and circulates as a major metabolite.

1,25(OH)₂D is the active hormone generated in the kidney.

The level of active hormone is subject to PTH, phosphate, FGF23, and feedback.

The source defines vitamin D deficiency using a circulating 25(OH)D measurement.

Robbins (11th ed.) states vitamin D deficiency at 25(OH)D < 20 ng/mL; Laboratory standards may vary.

Slide 66 · Mechanism-based interpretation of a deficiency pattern

Initial deficit

Compensated physiology

Vitamin D availability is reduced.

Intestinal calcium and phosphate uptake fall.

Serum calcium may decline initially.

PTH increases to defend extracellular calcium.

Renal phosphate loss can persist.

Insufficient phosphate limits osteoid mineralization.

These are directional pathophysiologic relationships, not a universal diagnostic laboratory profile.

Slide 67 · Teaching case: A child with progressive leg bowing

TEACHING SCENARIO

A walking child develops progressive tibial bowing and visible costochondral prominences. A history suggests limited sunlight exposure and low dietary vitamin D.

Which tissue defect best unifies the skeletal findings?

A. Failure of provisional growth-plate calcification

B. Normally mineralized but quantitatively depleted bone

C. Excessive cartilage-to-bone conversion

D. Primary mature-bone remodeling without plate involvement

Slide 68 · Case interpretation: Growth-plate failure

A — impaired provisional calcification at an open growth plate

REASON 1

Persistent cartilage and osteoid disorganize the metaphyseal junction.

REASON 2

Costochondral enlargement explains the rachitic rosary.

REASON 3

Weight bearing bends inadequately mineralized long bones.

Age, growth-plate status, and loading explain the pattern of rickets.

Slide 69 · Teaching case: Adult fractures without gross bowing

TEACHING SCENARIO

An adult with a condition affecting intestinal fat absorption develops skeletal fragility, including a femoral-neck fracture. Bone remodeling continues, but new matrix mineralizes inadequately.

Which pathologic lesion is most consistent with the scenario?

A. Persistent widened seams of unmineralized osteoid

B. Overgrowth of epiphyseal growth-plate cartilage

C. Preserved mineralization with primary loss of bone mass only

D. Brown tumors caused by autonomous PTH secretion

Slide 70 · Case interpretation: Osteomalacic osteoid

A — persistent unmineralized osteoid in the adult skeleton

REASON 1

Fat malabsorption can compromise vitamin D uptake.

REASON 2

New osteoid is produced but its mineral deposition is inadequate.

REASON 3

Fracture susceptibility does not require distortion of skeletal contours.

Bone quantity and bone mineral quality should be considered separately.

Slide 71 · Integrated pathogenesis: From supply to skeletal phenotype

Low vitamin D, inadequate calcium/phosphate, renal disease, or endocrine dysfunction compromises mineral availability.

PTH compensation may normalize calcium while perpetuating phosphate loss.

Open growth plates develop disordered endochondral ossification and deformity.

Closed growth plates leave an adult remodeling defect with osteoid accumulation and fractures.

The common denominator is impaired mineralization of newly formed matrix.

Slide 72 · Final synthesis: Two phenotypes, one mineralization problem

Rickets

Osteomalacia

Open growth plate is the key anatomic context.

Persisting cartilage and osteoid disrupt bone formation.

Skull, chest, limbs, and spine deform under stress.

New adult remodeling osteoid remains undermineralized.

Trabeculae have prominent unmineralized seams.

Vertebral and femoral-neck fractures are characteristic risks.

Ask first: Is the defect in bone mass or in mineralization?

Slide 73 · Core textbook references

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th ed. (2026).

Chapter 26 — Bones, Joints, and Soft Tissue Tumors: “Osteomalacia and Rickets,” p. 1072.

Chapter 9 — Environmental and Nutritional Diseases: Vitamin D metabolism, deficiency, rickets, and osteomalacia, pp. 400–403.

Original native PowerPoint schematics paraphrase these source mechanisms; no patient specimens, microscopy, or diagnostic images are represented.