is prevalent in underdeveloped nations and the resurgence of this condition in the developed areas is occurring due to immigrants. The organism is usually blood borne and originates from a focus of acute visceral disease during the final stages of primary infection. Direct extension and spread via draining lymphatics may also occur. Immunosuppressed individuals frequently have multifocal bone involvement. The spine followed by the knees and hips are the most common sites of skeletal involvement. This type of osteomyelitis tends to be more destructive and resistant to control than the pyogenic type. A number of complications can arise from this condition, namely, permanent compression fractures, neurologic defects secondary to spinal cord or nerve compression, tuberculous arthritis, sinus tract formation, and amyloidosis.
Osteogenesis Imperfecta
Osteogenesis imperfecta, or brittle bone disease, is a type 1 collagen disease caused by deficiencies in the synthesis of collagen. It is the most common inherited connective tissue disorder and primarily affects the bone and other tissues rich in collagen (eyes, ears, joints). It is usually an autosomal dominant mutation in the genes that encode the a-1 and a-2 chains of collagen. The genotype-phenotype relationship of the condition depends on the location of the mutation in the protein. Mutations causing a decrease in the amount of normal collagen are associated with mild skeletal abnormalities. More severe forms have polypeptide chains that cannot be arranged in the triple helix. Clinically, four major subtypes exist that vary in severity. Type 1 is compatible with life and has a decreased synthesis of pro-a1(1) chain and abnormal chains. This type is associated with postnatal fractures, skeletal fragility, hearing impairment, and joint laxity. Type 2 is lethal perinataly and the collagen defect is abnormally short pro-a1(1) chain or unstable triple helix. Death in utero or within days of birth, skeletal deformity with excessive fragility, and blue sclera are the major clinical features. Type 3 is progressive and is associated with growth retardation multiple fractures, dentinogenesis imperfecta, and progressive kyphoscoliosis. Finally, type 4 is associated with short pro-a2(1) chain defect and unstable triple helix and the major features include postnatal fractures, short stature, and moderate skeletal fragility.
Rickets
Rickets is a defective mineralization of bones before epiphyseal closure in humans due to deficiency of or impaired metabolism of vitamin D, phosphorus, or calcium. It is a disease of the growing bone and is unique to children and young adults. The primary cause is a vitamin D deficiency, but rarely, a dietary deficiency of calcium or phosphorus can also cause rickets. In a vitamin D deficiency state, hypocalcemia development leads to the production and secretion of excessive parathyroid hormone. This, in turn, causes a greater renal phosphorus loss. The excessive parathyroid hormone causes the decreased calcium levels to rise to normal values and the ALP, which is produced due to the overactive osteoblast cells, leaks into the ECF, causing elevation to very high levels. Also, recent studies have shown a correlation with increased fibroblast growth factor 23 and the development of rickets. Rickets leads to skeletal deformity and short stature. In females, pelvic distortion from rickets can cause problems with childbirth. Respiratory failure is a severe consequence. Thickening of the skull, frontal bossing, greenstick fractures, rickety myopathy, tetany, uncalcified osteoid at the metaphases, and weight-bearing deformities are all common clinical features.
Osteomalacia
Osteomalacia is the softening of bones caused by defective bone mineralization secondary to low levels of vitamin D, phosphorus, or calcium. Hyperparathyroidism causing hypercalcemia is contributory. This disease is the counterpart of rickets specific to adults. Causes can include a low dietary intake of the vitamin and minerals, not enough exposure to sunlight, malabsorption syndromes, and health conditions such as cancer, disorders of metabolism, kidney failure, and liver disease. The clinical features include aches and pains (symmetrical, non-radiating, sensitivity), muscle weakness, less rigid bones, and weight-bearing pathologies. Major biochemical findings include low serum calcium, low urinary calcium, low serum phosphate, and high ALP levels.
Bone-Forming Tumors
Bone tumors are diverse in their gross and microscopic features and vary in their natural history. Benign lesions greatly outnumber their malignant counterparts and occur mainly within the first three decades of life, whereas in the elderly, a bone tumor is more likely to be malignant. There is production of bone by neoplastic cells and the tumor bone is usually deposited as woven trabeculae and is mineralized. Bone tumors affect all ages and arise in virtually every bone, but most develop in the first several decades of life. Tumors have affinity to develop in the long bones of the extremities.
However, specific types of tumors target certain bones and age groups. The specific cause of bone tumors is unknown. However, genetic abnormalities play a significant role. For example, sarcomas occur in patients with hereditary retinoblastoma cancer, which linked to mutations in the genes coding for p53 and RB. Other bone neoplasms are also associated with conditions such as Paget’s disease, radiation, and metal prostheses. However, these types of neoplasms account for only a small number of tumors. Clinically, benign lesions are commonly asymptomatic and are detected through accidental findings. Other tumors present as pain or are noticed as a slow growing mass. More commonly, the tumor is detected by a sudden fracture. Radiological findings along with biopsy and histological studies are gold standard for diagnosis.
Acromegaly
Acromegaly is a syndrome in which there is an abnormality in the anterior pituitary gland, causing the release of large quantities of growth hormone. This results in abnormal growth of bone, especially in the mandible and the anterior portion of the skull. The overgrowth of the mandible results in malocclusion of the jaw, abnormal spacing of the teeth, and prognathism of the jaw. Due to the abnormal osteogenesis, the bone that is produced is of abnormal composition and structure. This can lead to arthritis.
Bone Fracture
Fracture of the bone is when any factor causes a break in the normal bone structure. This can occur due to trauma, and certain conditions can greatly increase the risk for this, including cancer, osteoporosis, and vitamin D and calcium deficiency. The fracture can result in loss of function of the bone marrow, such as hematopoiesis, or the loss of structural integrity. The fractured part of bone can also form an embolism if it enters a blood vessel.
Muhammad Saad Faiz
Arfa Faiz
Army Medical College, National University of Sciences and Technology
See Also: Bone: Cell Types Composing the Tissue; Bone: Current Research on Isolation or Production of Therapeutic Cells; Bone: Development and Regeneration Potential; Bone: Stem and Progenitor Cells in Adults.
Further Readings
Kumar, Vinay, et al. Robbins and Cotran Pathologic Basis of Disease, 8th ed. Philadelphia: Saunders/Elsevier, 2010.
Medscape. “Rickets.” http://emedicine.medscape.com/article/985510-overview (Accessed May 2014).
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