Musculo-skeletal System

Chapter 15 Musculo-Skeletal System



Bone 586

Bone Turnover 587

Osteoporosis 588, 589

Osteomalacia and Rickets 590

Metabolic Bone Disease 591

Paget’s Disease of Bone 592

Bone – Miscellaneous 593

Infections of Bone 594, 595

Developmental Abnormalities 595, 596

Tumours in Bone 597–599

Joint Disease 600

Joint Trauma 601

Osteoarthritis (OA) 602, 603

Rheumatoid Arthritis (RA) 604, 605

Sero-Negative Arthritis 606

Infections of Joints 607

Joint and Soft Tissues – Miscellaneous 608

Para-Articular Tissues – Miscellaneous 609

Collagen Diseases 610

Skeletal Muscle 611, 612

Atrophy and Hypertrophy 613

Neurogenic Atrophy 613, 614

Myasthenia Gravis 614

Muscle Damage 615

Muscular Dystrophy 616

Inherited Myopathies 617

Acquired Myopathies 618

Muscle Diseases – Diagnosis 619


Bone


There are two different forms of normal adult bone, both with a lamellar (layered) structure.


1. COMPACT BONE
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2. CANCELLOUS BONE
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Note: Cancellous bone comprises 20% of bone mass but 80% of bone turnover due to its large surface area


WOVEN BONE (non-lamellar), is a primitive form laid down in fetal development. In adult life, this type is seen in bone repair and bone-forming tumours. It can be remodelled to be replaced by lamellar bone.


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Bone and Calcium


Bone acts as a reservoir for calcium, which is maintained within a narrow range (2.1–2.6 mmol/l). Hypocalcaemia stimulates parathyroids to produce parathyroid hormone (PTH) which promotes bone resorption, calcium absorption from the gut and reabsorption from the kidney. As the serum calcium rises, PTH production is switched off.



Bone Turnover


Bone is formed by osteoblasts and removed by osteoclasts.


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Osteoblasts



– derived from osteoprogenitor cells.

– produce Type I collagen and other proteins.

– secrete alkaline phosphatase – a marker of bone formation.

– stimulated by mechanical stress, androgens, cytokines, e.g. TGF-β


Osteoclasts



– derived from marrow precursors.

– produce acid and enzymes to remove bone.

– produce collagen degradation products e.g. urinary HO proline – a marker of bone destruction.

– stimulated by cytokines e.g. IL-1, IL-6 (indirectly by PTH).

– inhibited by oestrogens.

The activities of the two cell types are closely ‘coupled’ in the normal process of bone turnover. In the adult 10% of the skeleton is replaced annually. The process has activating and inhibitory arms.



Activation


Osteoblasts bear RANKL (Receptor Activator of NF-κB Ligand)


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Inhibition


Under other circumstances osteoblasts and other cells produce osteoprotegerin (OPG) a soluble molecule which blocks activation through RANK.



Osteoporosis


OSTEOPOROSIS is the commonest disorder of bone. It is defined as a systemic disease characterised by:


(1) low bone mass.

(2) microarchitectural deterioration of bone, with

(3) an increase in bone fragility and susceptibility to fracture.

A patient is said to have osteoporosis if bone mineral density >2.5 standard deviations below the mean of normal young subjects.


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Clinical effects: – osteoporosis is a disease predominantly of post-menopausal females, but men are also affected.


1. It causes bone fractures (collapse) of vertebral bodies with loss of height and kyphosis.

2. Fracture of neck of femur or other long bones (especially Colles’ fracture of distal radius).

Note: In osteoporosis, the routine serum biochemical tests – particularly the calcium levels – are within the normal range.


Pathology: The changes in the vertebral bodies are shown.


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Note:


(i) The bone has a normal calcium content.

(ii) Bone loss is most marked in cancellous bone with its high turnover, but cortical bone is also affected.



Aetiology


In normal bone the dynamic processes of formation and resorption are in balance.


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In osteoporosis the balance is upset by


(1) diminished formation

(2) increased resorption, or both
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Bone mass decreases with age in both sexes: in old age, osteoblastic activity falls.


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PEAK BONE MASS is important – a high initial figure makes osteoporosis less likely. This depends on factors including:


(a) Genetic predisposition – polymorphisms of Type I collagen gene and other genes regulating bone cell activity.

(b) Nutrition – especially calcium intake.

(c) Exercise.

The aetiology can be summarised as follows:


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Localised osteoporosis is commonly due to disuse and is seen as a complication of other disorders, e.g. local immobilisation following fracture; limb paralysis and adjacent to severe joint disease with limitation of movement.



Osteomalacia and Rickets


Osteomalacia and rickets are disorders of bone due to failure of mineralisation of newly formed osteoid, caused by vitamin D deficiency in almost all cases. The poorly calcified bones are soft causing deformity or fracture.


Osteomalacia occurs in adult life and affects the osteoid which is being continually laid down in the normal remodelling of bone.


Rickets affects the growing child. As well as deformity and fractures, there is disturbance of growth plates. X-ray may show linear partial fractures of long bones which have failed to calcify (Looser’s zones).


The following simplified diagrams indicate the causes of vitamin D deficiency and its effects on bone.


Causes of deficiency:


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Effects on Bone



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Note: The hypocalcaemia seen in osteomalacia stimulates an increase in PTH levels and mild hyperparathyroidism.



Metabolic Bone Disease


In rickets the growing ends of long bones are abnormal.


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This results in stunting of growth and bowing of the lower limbs.


In females permanent deformities of the pelvis can cause serious difficulty during childbirth.


Enlargement of costochondral junctions gives the so-called rickety rosary



Hyperparathyroidism (see P.642)


Bone changes may be seen in hyperparathyroidism, especially when severe or long-standing. There is increased bone resorption due to PTH-induced osteoclastic activity. Due to ‘coupling’, osteoblastic activity is also increased but the net effect is bone loss.


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These changes affect all bones. There may be marked loss of bone with numerous osteoclasts and haemosidern pigment – the so-called ‘brown tumour of hyperparathyroidism’, which can mimic giant cell tumour.



Renal Osteodystrophy


Bone disease is common in chronic renal failure. It is a combination of osteomalacia and hyperparathyroidism, together with loss of bone synthesis.


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Paget’s Disease of Bone


This disease of unknown aetiology usually presents after the age of 50 years and is more common in males. It is fairly common (3% of autopsies), but only in its more severe forms are there clinical symptoms. The disorder is focal: the bones particularly affected are the pelvis, vertebrae, skull and lower limbs. It has been suggested that virus infection (e.g. measles, distemper) of osteoclasts is responsible. Genetic factors are important.


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To begin with, there is a localised increase in osteoclastic activity causing bone resorption; soon there is a marked osteoblastic reaction with bone resorption and deposition proceeding chaotically, so that irregular bone trabeculae with mosaic cement lines are formed. The bone may be thickened, but its structure is defective and weak. Biochemical changes reflect the cellular activity at trabecular level: Alkaline phosphatase ↑(osteoblastic); urinary hydroxyproline ↑(collagen destruction).


Often asymptomatic, the main effects are:


• Bone pain and deformity

• Pathological fracture

• Osteoarthritis (due to abnormal stresses caused by bone deformity)

• Nerve compression leading to deafness or spinal cord compression

• An increased risk (×30) of the development of bone sarcoma.

The use of bisphosphonates offers effective therapy in many cases.



Bone – Miscellaneous



Osteonecrosis (Avascular Necrosis)


Interruption of its blood supply causes bone to undergo necrosis. This tends to occur with fractures at sites where the vascular supply is damaged. Fractures of the femoral neck and scaphoid bone are good examples.


Non traumatic causes include corticosteroid therapy, alcoholism, sickle cell anaemia, Gaucher’s disease and historically in decompression in those working in increased atmospheric pressure (caisson disease).


Bone necrosis occuring at an articular surface often leads to degenerative arthritis.


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Note: These areas of necrotic bone may appear radiodense due to disuse osteoporosis of the adjacent living bone.


In children and adolescents osteonecrosis occurs at several epiphyseal sites probably due to trauma). The commonest is Perthes’ disease in which necrosis of one or both femoral heads occurs in children aged 4–10 years (male: female = 5:1).



Fibrous Dysplasia of Bone


This disorder may affect one (monostotic) or several (polyostotic) bones. On histology, well demarcated fibrous tissue containing small abnormal woven bone trabeculae is seen. Somatic mutations of the GNAS1 gene which encodes the α subunit of a stimulatory G-protein are responsible. Whether the disease is polyostotic or monostotic depends on the stage of development of the embryo when the mutation occurs, a state known as mosaicism.


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Complications


Fracture or deformity of the weakened bone.



Infections of Bone



Acute Osteomyelitis


Classically caused by Staphylococcus aureus. This affects the metaphyses of long bones in children. Nowadays the incidence has been greatly reduced and the use of antibiotics aborts the development of the disease. The bacteria are blood borne and settle in the cancellous bone of the metaphysis. The effects are dramatic and rapidly progressive.


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The presence of necrotic bone ensures that the inflammation continues.


The late complications are chronic osteomyelitis, disturbance of bone growth, amyloid disease may occur and occasionally squamous carcinoma arises in a sinus.


Other pyogenic bacteria can cause osteitis – the salmonella group (esp. S. typhi) and brucella, the latter often causing a low grade osteitis of the spine.


With inadequate antibiotic treatment, acute inflammatory processes may be converted into low grade osteitis. Staphylococcal infection of the spine may present in adults in this way.



Tuberculosis


The incidence of bone and joint infection parallels that of the more common pulmonary infection. It is therefore low in developed countries but still significant elsewhere, and has risen in association with HIV infection.


The spine and growing ends of long bones including the epiphyses are affected by blood borne spread and the infection spreads to the adjacent joints.


Bone is destroyed and replaced by granulomatous inflammation with caseous necrosis. Spinal infection spreads into adjacent tissues and leads to ‘cold abscess’ formation.


Although the progress is much less rapid than in acute osteomyelitis, without adequate treatment serious damage to bones and joints occurs.



Developmental Abnormalities


Generalised abnormalities are rare and usually inherited.


1. ACHONDROPLASIA is the commonest cause of dwarfism, with short, deformed limbs and a waddling gait. The bones at the skull base are underdeveloped.

A mutation of the fibroblast growth factor receptor gene (FGFR3) is responsible, which causes constitutive activation and inhibits cartilage growth. Although inherited as an autosomal dominant trait, 80% of cases result from new mutations.


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2. In OSTEOGENESIS IMPERFECTA (Brittle bone disease) the thin brittle bones fracture easily and a history of multiple fractures with minimal cause is the usual presentation. It is important to distinguish this from ‘non-accidental injury’.

The basic defect is in the osteoblasts which fail to synthesise collagen properly, due to mutations affecting the Type I collagen genes on chromosomes 7 and 17. The severity of the disorder depends on the type of mutation, some cases being lethal in utero.


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Patients may have:


(a) very thin sclerae which appear blue

(b) abnormal tooth development due to defective dentine formation.

3. OSTEOPETROSIS (Marble bone disease of Albers–Schönberg) is a disorder in which osteoclasts are absent or defective. This results in failure of bone remodelling and abnormal conversion of cartilage to bone. The whole skeleton becomes dense and the bones thickened, but weakened.

Complications are:


(a) anaemia due to failure of development of the bone marrow cavity

(b) fractures

(c) cranial nerve compression.

Bone marrow transplantation provides functioning osteoclasts and reverses the skeletal abnormalities.



Cysts of Bone


Simple bone cysts (unicameral-single chamber) have a thin fibrous lining and occur in the proximal humeral and femoral metaphyses of children. They often present with fracture.


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Jul 23, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Musculo-skeletal System

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