Brief Review on Metabolic Bone Disease

Abstract

Metabolic bone disease (MBD) is a broad term that describes a clinically heterogeneous group of diseases that are only united by a common denominator of an aberrant bone chemical milieu leading to a defective skeleton and bone abnormalities. From a forensic pathologist's perspective, MBDs create a challenging diagnostic dilemma in differentiating them from child abuse, particularly when the victim is an infant. Through this brief narrative review on MBD, bone pathophysiology and two relatively challenging pediatric MBDs will be discussed.

Keywords: Bone; Forensic pathology; Fracture; Metabolic bone disease; Osteogenesis imperfecta; Rickets.

Image 1:

1½ year old male infant with X-linked hypophosphatemic rickets. Frontal view of the right humerus shows widening and irregularity of the proximal physis (fraying). Frontal view of the right radius and ulna show fraying of the proximal and distal radial physis and widening of distal metaphyseal end of the ulna with cupping at the distal radial and ulnar metaphysis.

Image 2:

Frontal view of the femurs shows fraying and cupping in bilateral distal metaphysis with mild lateral convexity bowing deformity of bilateral femoral physis.

Image 3:

Frontal views of bilateral tibiae and fibulae show fraying and cupping of bilateral proximal and distal tibial and ulnar metaphysis with mild lateral convexity bowing deformity of the tibial and fibular physis.

Image 4:

Ten months after treatment, frontal view of the hands and wrists shows partial interval improvement of the fraying and cupping in bilateral distal radial and ulnar metaphysis.

Image 5:

Ten months after treatment, frontal view of the knees shows partial interval improvement of the fraying and cupping in bilateral distal femoral and proximal tibial metaphysis with lateral convexity bowing deformity of bilateral femora and tibiae.

Image 6:

Rickets bone changes. The epiphyseal plate is enlarged in height and width with marked and striking distortion of the hypertrophic cell zone (H&E, x200).

Image 7:

Base of the epiphyseal plate at the junction with the primary spongiosa. There is a poorly defined zone of provisional calcification; loss of the normal orderly columns and replacement by a marked increase in the axial height of the zone of hypertrophy. Note disorderly and profligate profusion of cells with a minimal amount of intervening matrix, failure of mineralization, and presence of vascular invasion. Only a few of the defective bars between the columns of chondrocytes and virtually no deposition of mineral is noted (H&E, x200). Note the tongues of viable cartilage without evidence of active enchondral ossification.

Image 8:

A) Normal growth plate with hypertrophic cartilage showing degeneration at the zone of calcification (degenerated cartilage highlighted by arrow). Note preserved cartilaginous matrix which is used by osteoblasts as a template to deposit osteoid and proceed with osteochondral ossification (H&E, x400). B) Normal growth plate in a newborn. Note the almost perfectly straight junction at the base of the growth plate and the primary spongiosa (highlighted by black line). Note ossification centers (blood vessels highlighted by short arrows) are away from the base of the growth plate. Note the distinct cartilaginous zone is formed by proliferative cartilage (highlighted by the long line), which is in contrast to rickets in which the bulk of the growth plate is formed by hypertrophic cartilage (H&E, x40)

Image 9:

Base of the epiphyseal plate at the junction with the primary spongiosa. There is a poorly defined zone of provisional calcification; loss of the normal orderly columns and replacement by a marked increase in the axial height of the zone of hypertrophy. Note disorderly and profligate profusion of cells with a minimal amount of intervening matrix, failure of mineralization, and presence of vascular invasion. Only a few of the defective bars between the columns of chondrocytes and virtually no deposition of mineral is noted (H&E, x200).

Image 10:

The medullary bone shows the bony trabeculae to be thin & irregular. There is a thick layer of unmineralized bone (osteoid seam – staining red)) surrounding the mineralized segment (staining green) (undecalcified bone Masson Goldner’s trichrome, x200).

Image 11:

The medullary bone shows the bony trabeculae to be thin & irregular. There is a thick layer of unmineralized bone (osteoid seam – staining red) surrounding the mineralized segment (staining green) (undecalcified bone Masson Goldner’s trichrome, x400).

Image 12:

A bony fracture with osteocartilagenous callus formation occurring in an infant with rickets. There is a central mass of hyaline cartilage within the callus and a periphery endochondral ossification, showing transition from osteoid to woven bone formation. (H&E, x200).

Image 13:

Acute fracture callus on the tibia of a 4-year-old (H&E, x200).

Image 14:

Organizing long bone fracture with osteocartilagneous callus formation. Note circle highlighting the cartilaginous callus (Masson trichrome, x400).

Image 15:

1-year, 8-months-old girl with type III osteogenesis imperfecta. The frontal view of the right lower extremity shows marked demineralization of the visualized bone structures. Marked lateral convexity bowing deformity of the femoral metaphysis is seen with multiple transverse sclerotic bands in the distal femoral and proximal tibial diametaphysis. An acute transverse fracture is visible through the mid femoral diaphysis. Ongoing healing fractures are seen in the mid diaphysis of the right tibia and fibula with the tibial fracture fixated with an intramedullary fixation road. Lateral view of the skull shows multiple wormian bones, especially at the lambdoid sutures.

Image 16:

Multiple wormian bones.

Image 17:

Same patient as seen in Image 16 at 11 years of age. Single view of bilateral upper extremities shows mild bowing deformity of bilateral humeral and radial diaphysis with diffuse demineralization and transverse sclerotic bands in bilateral distal radial and ulnar diametaphysis. There is posteroinferior dislocation of bilateral radiocapitelar joints.

Image 18:

Osteogenesis imperfecta gross examination picture of chest cage showing multiple intrauterine fracture calluses.

Image 19:

Osteogeneses imperfecta bone changes. A) There are angulated and distorted bones that are acquired from recurrent fractures that can start in-utero depending on the osteogenesis imperfect a type (H&E, x40). B) A severe form of osteogenesis imperfecta with the medullary cavity showing virtually no bony trabeculae but instead thin, sparse and non-connected spicules that are entirely formed of hyaline cartilage (H&E, x40).

Image 20:

Normal medullary bone in a newborn (H&E, x200). Note the thickness of the boney trabeculae compared to those in osteogenesis imperfecta. Also note the trabeculae to be formed mainly of bone with only a residual central core of hyaline cartilage templates. Compare to osteogenesis imperfecta which is almost entirely formed of hyaline carriage.

Image 21:

Osteogeneses imperfecta bone changes. A) A metadiphyseal subcortical microfrature with abundant cartilaginous fracture callus. Note thin disorganized surrounding bony spicules (H&E, x40). B) Abnormal growth plate with failure of formation of primary spongiosa with persistence of calcified cartilaginous bars in diaphysis type (H&E, x40).