Musculoskeletal disorders

Endochondrial ossification

Whilst the cranial bones of the skull and clavicle form from direct ossification from mesenchyme, the bones of limb and girdle form from ossification of a cartilaginous precursor of the long bones of the skeleton (a process known as endochondrial ossification). Condensation of lateral plate mesenchyme occurs in a rod-like structure along the axis of the limb bud. Cartilage cells (chondrocytes) respond to growth factors and differentiate (chondrification). These cells secrete proteoglycans and collagen to form cartilage. Initially there is deposition of cartilage around the entire limb condensations but then further chondrification is limited to future bone sites, sparing the interzone regions, resulting in the site of future joints.

Joint formation

For the joints of the long bones, mesenchymal cells at the interzones of long bones differentiate into multiple fibroblastic connective tissue layers. These then differentiate further to provide the articular cartilage at either end of the joint, and connective tissue in the middle forms the internal structures of the joint – synovial tissue, menisci and ligaments. Vacuoles form within the connective tissue which then becomes the joint cavity. The mesenchymal sheath becomes the joint capsule ( Fig. 27.1 ). Fibrous joints, or immobile joints which connect bones (e.g. in the skull, pelvis) are also developed from interzones, which differentiate into a single layer of fibrous connective tissue.

Primary ossification

Following chondrification, ossification occurs from the primary ossification centre. In response to growth factors, mesenchymal cells in this area differentiate into bone cells (osteoblasts). These cells secrete the calcium matrix of mineralized bone. Bone-resorbing osteoclasts also appear. These enable remodeling of growing bone, a process which continues throughout development into adult life.

Skeletal muscle

The limb musculature develops from two condensations of somitic mesoderm that in the 5th week invades the limb bud, one ventrally, the other dorsally. Ventral somatic mesoderm gives rise to mainly flexors, pronators and adductor muscles whilst dorsal somatic mesoderm dorsally gives rise to mainly extensors, supinators and abductor muscles. Cells in these condensations differentiate into myoblasts (muscle cell precursors). Myoblasts fuse together to form syncytia.

The innervation of the limb muscles develops from branches that develop from spinal nerve axons in a multistep process. Branches of the ventral spinal nerve innervate ventral muscles, and branches of the dorsal spinal nerve innervate dorsal muscles.

Limb defects

Limb defects can be grouped into three categories:

• 1.

  Reduction defects , in which the entire limb (amelia) or part of the limb (meromelia) is missing.

• 2.

  Duplication defects , in which there are extra limb elements. The commonest defect being the extra presence of digits (polydactyly).

• 3.

  Dysplasia (malformation) of the whole of any part of the limb. This includes fusion of digits (syndactyly) or excessive growth of parts of the limb (gigantism).

Limb defects can be broadly attributed to the following processes:

• Development arrest (failure to form)

• Failure of differentiation

• Duplication

• Overgrowth (hyperplasia)

• Undergrowth (hypoplasia)

• Focal defects, e.g. amniotic fluid band syndrome

• General skeletal abnormalities, e.g. osteogenesis imperfecta (see below)

Most limb defects have multifactorial aetiologies, from a combination of environmental and genetic influences, but either may predominate. Examples of conditions where genetic (familial) aetiologies predominate include most causes of polydactyly or ectrodactyly (absence of fingers or toes). Polydactyly is a relatively common finding in newborns, affecting 1 in 500 newborns. Over 100 genes have been described but most cases result from abnormalities in a single gene. Postaxial hand polydactyly is a common isolated disorder in Black African children, especially males, and autosomal dominant transmission is suspected. In contrast, postaxial polydactyly seen in white children is usually syndromic and associated with an autosomal recessive transmission.

Developmental dysplasia of the hip

The cause of developmental dysplasia of the hip (DDH) is not clear but it is usually multifactorial. Known risk factors include female gender, family history, oligohydramnios, breech position, and the presence of other congenital abnormalities, e.g. neuro­muscular disorders. In the normal development of the hip joint, the head of the femur is smooth and rounded, and the acetabulum is cup-shaped. However, in DDH there may be abnormalities of the shape of the head of the femur, the shape of the acetabulum or the surrounding structures. This means that the acetabulum and femur may not be in close contact. Depending on the degree of abnormality, the hip may be subluxed or dislocated.

Talipes equinovarus

Talipes equinovarus is a complex abnormality affecting 1 in 1000 live births. The entire foot is inverted and supinated, the forefoot adducted and the heel is rotated inwards and in plantar flexion. The affected foot is shorter and the calf muscles thinner than normal. The position of the foot is fixed, cannot be corrected completely and is often bilateral. It is more common in males (2 : 1) and can be familial but is usually idiopathic. However, it may also be secondary to oligohydramnios during pregnancy, a feature of a malformation syndrome or of a neuromuscular disorder such as spina bifida. The Ponseti method for correction is a manipulative technique involving serial casting and usually avoids the need for invasive surgery. Talipes equinovarus needs to be differentiated from positional talipes, where the foot is of normal size, the deformity is mild and can be corrected to the neutral position with passive manipulation, and the rare congenital vertical talus , where the foot is stiff and rocker-bottom in shape. Many of these infants have other malformations.

Environmental causes of limb defects

Spine defects

Congenital structural defects of the spine may occur secondary to failure of vertebrae formation, separation or fusion, e.g. abnormal induction of the sclerotome and the neural tube. Depending on the position of the abnormality, the spine may develop to the left or right (scoliosis), or convex overcurvature (kyphosis) or sway backwards (lordosis). Growth potential depends on the involvement of the vertebra growth plate and gives rise to the differences in progression and deformity.

Congenital scoliosis is the most common developmental spine condition. Although the aetiology is not fully understood, failure of sclerotome segmentation results in vertebrae that are abnormally connected on one side, causing asymmetrical growth rates. There may also be disruption of the normal shape of the vertebra causing a wedge shape. Similarly, asymmetrical growth may occur. This is different to idiopathic scoliosis, which presents with either early onset (less than 5 years old) or late onset. The most common presentation is late-onset idiopathic scoliosis, mainly in girls 10–14 years of age during their pubertal growth spurt. Secondary scoliosis is common and related to other disorders that result in neuromuscular imbalance, e.g. cerebral palsy, muscular dystrophy, polio; disorders of bone or cartilage, such as neurofibromatosis, Marfan's syndrome; or leg length discrepancy. If a child has a congenital vertebral abnormality, other systems should be investigated to exclude syndrome characteristics, e.g. VACTERL association.

Joint defects

Arthrogryposis is the collective term for a number of conditions associated with joint contractures at birth. Factors that inhibit normal joint development or movement (extrinsic or intrinsic) can result in joint contractures. Extrinsic factors may include environmental problems, such as oligohydramnios or viral infections. Intrinsic factors include underlying genetic/molecular abnormalities leading to connective tissue, muscle or neurological abnormalities. Arthrogryposis is divided into three main categories:

• Amyoplasia: muscle weakness and multiple severe joint contractures

• Distal: contractures affecting the hands and feet

• Syndromic: associated with congenital neurological or muscle disease

Bones

At birth, the diaphyses (‘shafts’) of the long bones are completely ossified, whereas the epiphyses (‘ends’) remain cartilaginous. Secondary ossification centres arise from the epiphyses, resulting in the ends gradually ossifying. Growth of the long bones relies on proliferation of chondrocytes in the epiphyseal cartilaginous plate (growth plate), which persists between the epiphysis and growing end of diaphysis (metaphysis). The epiphyses and diaphysis fuse around the age of 20 years. During childhood, if trauma occurs to the growth plate, the growth of that limb may be affected.

During the ossification process, bone is invaded by numerous blood vessels, which branch from the limb vasculature. A dominant nutrient artery develops, which nourishes the bone. During life, if this nutrient vessel becomes interrupted then cellular death of bone components occurs (avascular necrosis) and if this involves the bones around a joint, the articular surface may become damaged (osteochondritis dissecans). The blood supply in certain areas is vulnerable. Osteochondroses are a group of conditions in which the primary or secondary ossification centre undergoes avascular necrosis, and there is resorption of old dead bone, with replacement of new bone tissue. Examples include:

• Perthes disease – femoral head

• Osgood–Schlatter disease – tibial tubercle

• Freiberg disease – second metatarsal head

• Thiemann disease – phalangeal epiphyses

• Scheuermann disease – lumbar or midthoracic

• Köhler disease – navicular tarsal

Legg–Calvé–Perthes, or Perthes disease, is one of the most common of the osteochondroses, most often seen in young boys (age range: 4–8 years; male : female ratio: 4.5 : 1). Interruption of the blood supply causes avascular necrosis of the capital femoral epiphysis of the femoral head, and is followed by revascularization and reossification over 18–36 months. Slipped capital femoral epiphysis (SCFE) results in displacement of the epiphysis of the femoral head posteroinferiorly, requiring prompt treatment in order to prevent avascular necrosis. It is most common at 10–15 years of age during the adolescent growth spurt, particularly in obese boys, and is bilateral in 20%.

The cause of the osteochondroses is not clear, but they may be associated with trauma, especially at sites where vascular supply to the bone is vulnerable (e.g. femoral head) or follow a transient synovitis (e.g. Perthes disease after an irritable hip) or can be associated with metabolic endocrine abnormalities (e.g. hypothyroidism and hypogonadism in slipped capital femoral epiphysis (SCFE)).

Bone remodeling

Bones consist of two cell types, osteoclasts (bone-resorbing cells) and osteoblasts (bone-forming cells). These act together to control bone growth and metabolism through the bone remodeling cycle. Each remodeling cycle takes several weeks to complete. In childhood, resorption and formation usually occur at the same rate, except when extra bone matrix is required for growth (for example, during skeletal development). In pathological situations, increases in bone resorption or decreases in bone formation may result in an overall net loss of bone (osteoporosis). Inadequate mineralization of the bone matrix (osteomalacia) can cause bone deformity if it occurs in a growing skeleton (rickets). Osteoporosis may be classified into primary or secondary causes.

Primary osteoporosis

There are two main types of primary osteoporosis. Idiopathic juvenile osteoporosis may present pre/early puberty with metaphyseal and vertebral crush fractures. Osteogenesis imperfecta presents at any age with varying degrees of severity. The principal features include bone fragility and low bone mass.

Case history

Osteogenesis imperfecta

A 6-month-old was taken to the emergency department by his parents due to inconsolable crying. He was found to not be moving his right leg and an X-ray confirmed a fractured femur. X-rays revealed several other fractures in various stages of healing. His parents could not explain what may have caused them. He was referred to the safeguarding team with suspected non-accidental injury. Subsequent investigations revealed a mutation in the COL1A1 gene.

• This baby had osteogenesis imperfecta (type I).

• Osteogenesis imperfecta is a group of inherited (autosomal dominant and recessive, although may be sporadic) abnormal collagen conditions.

• Mutations in COL1A1 and COL1A2 result in abnormalities in the production of alpha chain of type 1 collagen, the major protein found in bones, ligaments and tendons.

• Abnormal collagen metabolism causes bone fragility, with bowing, frequent fractures and hypermobility.

• In the most common form (type I), which is autosomal dominant, there are fractures during childhood, a typical blue appearance to the sclerae, and some develop hearing loss. Treatment with bisphosphonates reduces fracture rates. Fractures require careful management to minimize joint deformity. Prognosis is variable.

• There is a severe, lethal form (type II) with multiple fractures already present before birth. Many affected infants are stillborn. Inheritance is variable but mostly autosomal dominant or due to new mutations.

• In other types, scleral discoloration may be minimal.

Secondary osteoporosis

Secondary osteoporosis can result from inflammatory conditions (e.g. inflammatory bowel disease, juvenile idiopathic arthritis (JIA), cystic fibrosis, prolonged use of glucocorticoids or following disuse (e.g. cerebral palsy, muscular dystrophies, immobility) and in children and young people with endocrine disturbances (e.g. thyroid disease and hypogonadal states).

Osteomalacia/rickets

Most cases of osteomalacia are due to lack of vitamin D (see later in this chapter), resulting from poor sunlight exposure or dietary inadequacy. Osteomalacia is more common in darker-skinned individuals living in colder climates. Vitamin D deficiency results in myopathy and MSK aches and pains. Infants are usually miserable, and other features can include bowed limbs, metaphyseal swelling, bossed forehead and bone pain. Inherited forms of rickets include X-linked hypophosphataemic rickets, and children with McCune–Albright syndrome/polyostotic fibrous dysplasia.

Osteopetrosis (marble bone disease)

In this rare disorder, there is increased bone mass due to failure to resorb bone – the bones are dense but brittle. The severe autosomal recessive disorder presents with faltering growth, recurrent infection, hypocalcaemia, anaemia and thrombocytopenia (due to bone marrow failure). Prognosis is poor, but bone marrow transplantation can be curative. A less severe autosomal dominant form may present during childhood with fractures.

Skeletal dysplasias

Skeletal dysplasias are a group of clinically and genetically heterogeneous disorders causing generalized abnormalities of bone growth and/or bone modeling. Most are rare and usually present with one or more of:

• Short stature (usually disproportionate). If the limbs are short, it is important to note which segment(s) are affected:

  • –

    Proximal segment (shoulder to elbow, or hip to knee) – rhizomelic

  • –

    Middle segment (elbow to wrist, knee to ankle) – mesomelic

  • –

    Distal segment (hands, feet) – acromelic, or all segments micromelic

• Bone deformity/joint malalignment, including skull shape and circumference, face with dysmorphic features, spine (including scoliosis and kyphosis), limb and digit abnormalities

• Recurrent fractures usually after minimal trauma

• Associated features, including abnormalities of vision, hearing, teeth, palate, heart, abdominal organomegaly, development, neurological function.

Joint problems

Joints may be classified by their movements and tissues. Synovial joints (diarthroses) move freely, have a fibrous joint capsule and distinct joint cavity. There are several distinct subtypes including:

• Ball and socket – hip, shoulder

• Hinge – elbow, knee

• Saddle – thumb

• Gliding – intercarpal

• Condyloid – wrist

Synovial joints are lined with a highly vascular synovial membrane. Synovial fluid is produced naturally to lubricate the joint but can be produced in excess if the synovial membrane becomes inflamed (synovitis – see juvenile idiopathic arthritis, JIA). The blood supply of the bone is an important factor in the presence of infection such as septic arthritis, as it can lead to bone destruction and usually results from haematogenous spread, especially in neonates and young children, where spread from adjacent osteomyelitis into joints can occur where the capsule inserts below the epiphyseal growth plate. Other problems may arise in joints due to disruption of supportive cartilage (e.g. meniscal problems at the knee) or ligaments.