Bone destruction

OA is often divided into primary (idiopathic) and secondary disease (Table 55-1). Primary OA is the predominant form and occurs in the absence of a precipitating event. It may assume a localized, generalized, or erosive pattern. Localized OA is distinguished from generalized disease by the number of sites involved, whereas erosive disease is characterized by an erosive pattern of bone destruction and marked proliferation of interphalangeal joints of the hands. Secondary OA occurs when the disease is caused by congenital or developmental disorders or inflammatory, metabolic, or endocrine diseases. 

Treatment of osteomyelitis is dependent on the extent of bone necrosis. For acute osteomyelitis with minimal bone destruction, an extended course of antimicrobial therapy should effectively treat the infection however, in chronic osteomyelitis surgical intervention is also typically required. 

Most commonly used for initial screening -Bone destruction is not apparent for 10 to 21 days following infection... 

Radiograph lytic changes consistent with bone destruction... 

Elevated alkaline phosphatase may indicate bone destruction. 

Gravallese EM. Bone destruction in arthritis. Ann Rheum Dis 2002 61(Suppl 2) ii84—86. 

Joosten LA, Lubberts E, Helsen MM, et al. Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis. Arthritis Res 1999 1(1) 81—91. 

Calcium should be ingested in adequate amounts to prevent secondary hyperparathyroidism and bone destruction. Although calcium increases BMD, fracture prevention is minimal. It should be combined with vitamin D and osteoporosis medications when needed. 

Penicillamine is an analog of cysteine. Only the d-isomer is used. In patients with progressive rheumatoid arthritis which is refractory to treatment with gold compounds it may retard progression of articular cartilage and bone destruction. For these effects to become apparent a latency period of 3 4 month often is needed. Its mechanism is unknown but it supposedly interferes with the synthesis of DNA, collagen and mucopolysaccharides. 

The amount of calcium deposited tit bone at any moment may be determined from experiments with radioactive calcium. In grow ing individuals, it exceeds the amount removed by bone destruction. In adults, it is about the same as the amount removed. Such individuals arc considered to be in "zero" calcium balance. In older persons. Ihe amount deposited is less than the amount removed. 

Osteolytic bone diseases or bone resorption the most important clinical application of BPs is as inhibitors of osteolytic bone diseases, including osteoporosis, tumor-related bone destruction, and Paget s disease. These are discussed in detail in the next section. 

Osteolytic tumors may induce bone destruction either through local invasion, or by a secondary metastatic bone disease. The most frequent types of primary tumors that develop into metastatic bone disease are, in the order of prevalence breast, prostate, thyroid, kidney, and bronchial tumors, whereas esophageal, gastrointestinal and rectal tumors are much less metastatic [11]. Very often, the destruction of bone in a metastatic bone disease leads to hypercalcemia of malignancy, which also responds to BPs. In addition, hematological cancers such as... 

Alkaline phosphatase (ALP) Liver kidney, bone, placenta, intestine, biliary epithelia 30-300 lU/L (higher in children due to increased bone growth) Raised levels may indicate biliary inflammation/ obstruction, malignant infiltration, cirrhosis, bone destruction, Paget s disease... 

M and 1.1 x 10 M respectively. In addition WF 14861 inhibited mouse crude bone cathepsin with IC50 value of 4.0 x 10 M. The compound ameliorated the tissue damage and the bone destruction modes of low calcium diet fed mouse and adjuvant arthritis rat model. It lowered the plasma calcium concentration from 11.70 0.33 mg/dl to 9.88 0.57 mg/dl (84.0 4.87 %) when injected at the concentration of lOOmg/kg to low calcium diet fed mice [72]. 

Much has been written about the value of urinary hydroxyproline elevations in separating bone formation from bone resorption. Correlations have been attempted clinically between urinary hydroxyproline, on the one hand, and serum alkaline phosphatase, serum and urinary calcium, calculations of calcium turnover such as the bone formation rate and bone resorption rate, bone histology, and bone radiology. Most authors feel that the level of urinary hydroxyproline refiects bone destruction (B6, B16, D8, D9, Gl, K26, L8, SI 6) more than bone formation (H9, K20). This does not seem to be a very useful argument clinically, because bone formation and destruction are usually occurring simultaneously in... 

Middle ear adenomas (MEAs, also known as carcinoid tumors and neuroendocrine adenomas) are distinctly uncommon tumors that affect both sexes equally and occur over a broad age range (14 to 80 years) with an average of about 40 to 45 years. > The most common complaints are unilateral hearing loss, tinnitus, and fullness in the ear. Otorrhea and pain are uncommon. On imaging, the tumor is always extraosseous with no evidence of bone destruction. 

Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease. J Clin Invest 108 1833. 

The humoral hypercalcemia of malignancy hypothesis states that an osteolytic non-PTH substance is secreted by certain tumors and, in an endocrine manner, is transported from tumor to bone through the bloodstream. The evidence for this hypothesis is that 1) bone destruction occurs in patients without bone metastases, 2) serum PTH levels in these patients were usually normal, 3) PTH mRNA was absent in tumors (27), and 4) tumor extracts from hypercalcemic patients enhanced bone cell adenylate cyclase activity and phosphate transport in kidney epithelial cells (28-30). 

Sabino MAC et al. Simultaneous reduction in cancer pain, bone destruction, and tumor growth by selective inhibition of cyclooxygenase-2. Cancer Res 2002 62 7343-7349. 

Hasturk H., Kantarci A., Ohira T, Arita M., Ebrahimi N., Chiang N., Petasis N. A., Levy B. D., Serhan C. N., Van Dyke T. E. 2006. RvEl protects from local inflammation and osteoclast-mediated bone destruction in periodontitis. FASEB Journal. 20(2) 401 03. 

Tai N, Kuwabara R Kobayashi M, Yamada R Ono T, Seno R Gahara Y, Ishizaki J, Hori Y (2010) Cytosolic phospholipase A2 alpha inhibitor, pyrroxyphene, displays anti-arthritic and anii-bone destructive action in a murine arthritis model. Tnflamm Res 59 53-62... 

The mechanism responsible for osteoporosis resulting from immobilization is not clear. One theory suggests that muscular activity stimulates osteoblastic activity in the bone. Another theory proposes that the rate of bone destruction is accelerated in osteoporosis. In immobilized innervated rat limb, there is an increased destruction in the matrix, reflected by a more rapid turnover of [ " C]glycine into the soft tissue. The increased turnover of amino acids into the protein of soft tissue is paralelled by an increased turnover by the calcium in the bone and the in the chondroitin sulfate. 

While MRI is unsurpassable in the detection of bone marrow infiltration, it does not allow for precise assessment of bone destruction, which is predictive for the risk of fracture. In order to prevent for potentially catastrophic pathologic fracture, it is most important to assess the fracture risk and initiate prophylactic stabi-hzation, if required. MDCT is most useful in the precise assessment of the extent of bony destructions and thereby in the prediction of fracture risk. 

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