Metabolic Bone Disorders

Metabolic bone disorders-I

Dr. Mehzabin Ahmed

Bone is a mineralized connective tissue consisting of organic matrix and inorganic elements. Calcium salt is the mineral. Unmineralised bone is known as osteoid. Organic matrix of the bone consists of: Bone forming cells including osteoprogenator cells, osteoblasts and osteocytes.  Osteoclasts are responsible for bone resorption, which are derived from monocytes macrophage precursors.  Proteins in the bone is mainly type I collagen. 

Bone is constantly being refashioned or remodeled by osteoblastic new bone formation and osteoclastic removal of old bone. Combined activity of osteoblasts and osteoclasts can produce re-shaping of bone in order to meet new directional stresses. Several factors are involved in bone formation and destruction: Parathyroid hormone (PTH)  ↓ Plasma Ca+ → ↑ PTH → bone resorption  Vitamin D → promotes mineralisation of the bone  Calcitonin → opposite effects of PTH  Other factors are – GH, corticosteroids, androgens, estrogens, and insulin. 

Common Metabolic Disorders of Bone Disorder of chondrocytes = abnormal cartilage  Achondroplasia  Mucopolyssacharidoses Disorder of osteoblasts = abnormal bone matrix  Osteogenesis Imperfecta  Osteoporosis Disorder of Osteoclast function = abnormal remodeling  Osteopetrosis  Paget Disease  Osteitis fibrosa cystica (Hyperparathyroidism) Disorders of mineralisation = inadequate calcification  Rickets/ Osteomalacia  Renal Osteodystrophy

Disorders of bone mineralization Osteomalacia Occurs due to failure of mineralisation of osteoid, due to vitamin D deficiency in adults. It results in bone pain, micro factures of cortical plate and trabecular bone. The cortical microfractures are seen radiologically and are known as ‘Looser’s zone’ and are most common in the bones of the lower limbs. Severe long-standing untreated osteomalacia results in bowing of legs. Causes: - Because of vitamin D deficiency, which is required for mineralisation of the bones.

Vitamin D deficiency is due to 

Inadequate dietary intake

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Inadequate body synthesis of vitamin

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Malabsorption due to intestinal diseases

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Renal diseases

Disorders of bone mineralization Renal osteodystrophy Refers to metabolic and structural abnormalities of bone caused by presence of chronic renal failure. There are two main components to renal ostrodystrophy: a) Osteomalacia of renal origin → due to failure of conversion of 25 hydroxy vitamin D3 to the active principle 1,25 dihydroxy vitamin D3 in the kidney because of tubular damage. b) Secondary hyperparathyroid effects – secondary to low calcium because of a combination of vitamin D deficiency, excess calcium loss in urine and phosphate retention. The bone in renal ostrodystrophy therefore shows combination of secondary hyperparathyroid changes, excessive bone erosion by osteoclasts and failure of mineralisation of osteoid collagen

Chronic renal failure Deficiency of active to form of Vitamin D

Hyperparathyroidism due calcium loss, Vitamin D def & Phosphate retention

Deficient mineralization

 osteoclastic activity

Osteomalacia

Erosion of the bone

Disorders of chondrocytes/ chondroid matrix Achondroplasia Mucopolysaccharidoses Mutation in FGFR3 (fibroblast growth factor receptor 3) gene

Lysosomal storage disorders - Deficiency in the acid hydrolases required to degrade cartilage matrix Hurler and Hunter disease - Abnormality in hyaline cartilage

Disorders of osteoblasts/ osteoid matrix Osteogenesis imperfecta Congenital defect in the collagen synthesis resulting in abnormally fragile bones and teeth and blue sclera

Disorders of osteoblasts/ osteoid matrix Osteoporosis is characterized by generalized reduction in the mass of bone. It is the most common metabolic disease of the bone. The bone is composed of abnormally thin trabeculae. The condition is common in elderly Causes: 

Senile osteoporosis encountered in the menopausal women. Estrogen is required for the maintenance of the bone mass

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Prolonged corticosteroid therapy

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Cushing syndrome

Senile osteoporosis KYPHOSIS

Compression #

Wedge #

Clinical features Bone pain – back pain Compression fracture of one of more vertebral bodies Overall loss of height because of compressions of vertebrae Kyphosis (bending of the spine anterioposteriorly) Fractures of neck of femur and wrists are common complication following trivial injury

Metabolic bone disorders-II

Disorders of osteoclasts/ bone remodelling

Osteopetrosis Genetic disorders due to reduction in osteoclastic bone resorption due to Osteoclast dysfunction Also known as ‘Marble Bone disease’

Disorders of osteoclasts/ bone remodelling

Osteopetrosis Bones are brittle like chalk and fracture easily Bones are bulbous and misshapen Bones do not develop a medullary cavity No place for Hemopoietic tissue to develop Extramedullary hemopoiesis continues with hepatosplenomegaly Patient develops anemia, infections and tendency to bleed Narrow neural foramina may compress exiting nerves

Disorders of osteoclasts/ bone remodelling

Paget’s diseases

In Paget’s disease there is excessive uncontrolled resorption of bone by abnormal osteoclasts. Excessive osteoclastic activity results in localized destruction of bones followed by an uncoordinated osteoblastic response, producing new osteoid in an attempt to fill the defects. Both osteoclastic and osteoblastic responses are random, haphazard and unrelated to the functional stresses on the bone. There is increase bone bulk but it is weaker than normal

Paget’s disease may be widespread, affecting many bones, or may be confined to one area in a single bone. Etiology is not known.

Clinical effects •Bone pain •Bone deformity – •Enlargement of the skull, • Thickening, and enlargement and bowing of the tibia. •Nerve compression symptoms are usually seen in association with Paget’s disease of the skull. •Pathological fractures Mosaic of cement lines

•Malignant tumor – Osteosarcoma

Disorders of osteoclasts/ bone remodelling Hyperparathyroidism Produces bone erosion by stimulation of osteoclastic activity. Normally PTH stimulates osteoclastic resorption of bone, with the release of calcium from the bone into the plasma. Its activity is normally finely controlled by a feed back mechanism. Failure of the feed back mechanisms leads to excessive Parathormone secretion with continuing PTH output and excessive osteoclastic destruction of bone.

Two patterns of hyperparathyroidism: Primary hyperparathyroidism is because of an autonomous parathyroid tumor, usually a parathyroid adenoma, secrets excess PTH continuously outside of the control of the feed back mechanism. In secondary hyperparathyroidism a persistently low serum calcium level (due to excess Ca+ loss in the urine in chronic renal disease) leads to continuous stimulation of the parathyroids by the feedback mechanism this results in hyperplasia of all the parathyroid glands and a constant excessive secretion of PTH.

Effects of bone of constant PTH stimulation are 

uncontrolled absorption of bone

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followed by compensatory attempts by osteoblasts to deposit new bone,

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in addition to affecting all bones single or multiple focal osteolytic lesions are also present in bone.

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These osteolytic lesions appear as soft, semi fluid brown material because of old and recent hemorrhages called as ‘brown tumors’.

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Multiple brown tumors produce numerous osteolytic lesions in many bones know as ‘Von Recklinghousin’s disease’ of bone or osteitis fibrosa cystica’

At the end of the lesson on Metabolic Bone Diseases , the student should be able to: Describe briefly the composition of bone Explain the terms bone modeling, remodeling, woven bone, lamellar bone, osteoid. List the factors involved in bone metabolism Enumerate metabolic bone disease Briefly explain the pathologenesis, pathological features and clinical manifestations of’       

Osteopetrosis Osteomalacia, rickets Paget’s disease Hyper parathyroidism Renal osteodystrophy Osteoporosis Osteogenesis imperfecta and achondroplasia

Discuss the role of physical therapy in the management of metabolic bone disease