Osteitis fibrosa cystica

Osteitis fibrosa cystica (/ˌɒstiˈaɪtɪs faɪˈbroʊsə ˈsɪstɪkə/ OS-tee-AY-tis fy-BROH-sə SIS-tik-ə), is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue (peritrabecular fibrosis), and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica, abbreviated OFC, also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone (not to be confused with von Recklinghausen's disease, neurofibromatosis type I), is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss. Osteitis fibrosa cystica (/ˌɒstiˈaɪtɪs faɪˈbroʊsə ˈsɪstɪkə/ OS-tee-AY-tis fy-BROH-sə SIS-tik-ə), is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue (peritrabecular fibrosis), and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica, abbreviated OFC, also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone (not to be confused with von Recklinghausen's disease, neurofibromatosis type I), is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss. First described in the nineteenth century, OFC is currently detected through a combination of blood testing, X-rays, and tissue sampling. Before 1950, around half of those diagnosed with hyperparathyroidism in the United States saw it progress to OFC, but with early identification techniques and improved treatment methods, instances of OFC in developed countries are increasingly rare. Where treatment is required, it normally involves addressing the underlying hyperparathyroidism before commencing long-term treatment for OFC—depending on its cause and severity, this can range from hydration and exercise to surgical intervention. Osteitis fibrosa cystica is defined as the classic skeletal manifestation of advanced hyperparathyroidism. Under the ICD-10 classification system, established by the World Health Organization, OFC is listed under category E21.0, primary hyperparathyroidism. The major symptoms of OFC are bone pain or tenderness, bone fractures, and skeletal deformities such as bowing of the bones. The underlying hyperparathyroidism may cause kidney stones, nausea, constipation, fatigue and weakness. X-rays may indicate thin bones, fractures, bowing, and cysts. Fractures are most commonly localized in the arms, legs, or spine. The addition of weight loss, appetite loss, vomiting, polyuria, and polydipsia to the aforementioned symptoms may indicate that OFC is the result of parathyroid carcinoma. Parathyroid carcinoma, an uncommon cancer of the parathyroid glands, is generally indicated by serum calcium levels higher than usual, even in comparison to the high serum calcium levels that OFC generally presents with. Symptoms are also often more severe. Generally, the presence of a palpable neck mass is also indicative of the cancer, occurring in approximately 50% of sufferers, but virtually nonexistent in individuals with OFC with a different origin. Osteitis fibrosa cystica is the result of unchecked hyperparathyroidism, or the overactivity of the parathyroid glands, which results in an overproduction of parathyroid hormone (PTH). PTH causes the release of calcium from the bones into the blood, and the reabsorption of calcium in the kidney. Thus, excess PTH in hyperparathyroidism causes elevated blood calcium levels, or hypercalcemia.There are four major causes of primary hyperparathyroidism that result in OFC: The vast majority of cases of hyperparathyroidism are the result of the random formation of benign, but metabolically active, parathyroid adenoma swellings. These instances comprise approximately 80–85% of all documented cases of hyperparathyroidism. Approximately 1 in 10 documented cases of hyperparathyroidism are a result of hereditary factors. Disorders such as familial hyperparathyroidism, multiple endocrine neoplasia type 1 (MEN Type 1) and hyperparathyroidism-jaw tumor syndrome can, if left unchecked, result in OFC. MEN Type 1 is an autosomal dominant disorder and the most common hereditary form of hyperparathyroidism, affecting about 95% of genetic cases of OFC, and also tends to affect younger patients than other forms. Major mutations which can lead to hyperparathyroidism generally involve the parathyroid hormone receptor, G proteins, or adenylate cyclase. Certain genetic mutations have been linked to a higher rate of parathyroid carcinoma occurrence, specifically mutations to the gene HRPT2, which codes for the protein parafibromin. Parathyroid carcinoma (cancer of the parathyroid gland) is the rarest cause of OFC, accounting for about 0.5% of all cases of hyperparathyroidism. OFC onset by parathyroid carcinoma is difficult to diagnose.