Edit concept Create issue ticket

Osteitis Fibrosa Cystica

Von Recklinghausen's Disease of Bone

Osteitis fibrosa cystica (OFC) is a disease of the bone resulting from overproduction of parathyroid hormone. An excess of parathyroid hormone causes increased bone osteoclastic activity, and consequently, breakdown of the bone. 


Presentation

Sylavunus was the first to make a diagnosis of hyperparathyroidism in 1973, while Recklinghausen was the first to describe the bony changes seen in OFC [14].

The clinical manifestations of OFC include both the bone lesions and the features of hyperparathyroidism, the later causes nausea, urinary frequency, constipation, and fatigue. OFC causes bone pain and renders the bones susceptible to fractures. Common sites of fractures in OFC are the bones of the arms, leg, and spine. The skeletal changes in OFC are the most prominent of changes at the sites of increased bone activity: phalanges, skull bones, ends of long bones, and trabecular bones of the vertebrae.

Advanced OFC gives rise to brown tumors, which may appear as unifocal or multifocal lesions. Brown tumors are seen in advanced stages of hyperparathyroidism. Brown tumors appear to be more severe in young adults with a particularly high risk of recurrence. Brown tumors are seen in the base of the skull, paranasal sinuses, orbits, and spine. It affects the mandible more than the maxillae and it has also been observed to affect the nasal cavity, palate, and temporal bone [15]. Diagnosis of brown tumors involves clinical, laboratory, and radiological findings [16]. Histologically, brown tumors are characterized by the presence of extensive vascular fibroblastic stroma and numerous multinucleated giant cells which appear like osteoclasts [17].  

Hunting
  • The benign cytomorphologic features of brown tumor should not be overlooked or be considered nondiagnostic in the hunt for suspected malignancy.[ncbi.nlm.nih.gov]
Subcutaneous Mass
  • After the initial biopsy, a subcutaneous mass developed in the left thigh. Microsections of the biopsied mass disclosed adult T-cell leukaemia (ATL) neoplastic cells.[ncbi.nlm.nih.gov]
Bone Disorder
  • Introduction Clinical definition a metabolic bone disorder secondary to severe hyperparathyroidism Background parathyroid hormone (PTH) plays an important role in calcium homeostasis via increasing RANK ligand (RANKL) expression on osteoblasts to subsequently[step1.medbullets.com]
  • A bone disorder characterized by an increase in porosity, reduction in bone mass, increased bone fragility, and an increased risk of fractures. Primary vs.[studyblue.com]
  • "Chronic kidney disease mineral and bone disorder in children" . Pediatric Nephrology . 23 (2): 195–207. doi : 10.1007/s00467-007-0671-3 . PMC 2668632 . PMID 18046581 .[en.wikipedia.org]
  • Radiographic findings in renal osteodystrophy depend on the type of bone disorder and are not sensitive.[gamma.wustl.edu]
Chest Deformity
  • She was receiving vit D occasionally, and for a long period of time was suffering from the pain in the lumbar spine, other bones, large joints, and progressing chest deformity.[bone-abstracts.org]

Workup

Baseline blood investigations for the diagnosis of OFC include serum calcium, PTH, and alkaline phosphatase levels. All of these indices may be high with low serum phosphorus.

Imaging studies play key roles in the diagnosis of OFC. Plain radiographs of bones are useful and may show thin bones, bowing, cysts, and fractures. The lesions are characterized by well-defined areas of radiolucency with cortical expansion accompanied with bone destruction [18]. Furthermore, the best diagnostic means of secondary hyperparathyroidism is to conduct parathyroid immunoassay and evaluation to confirm CRF [19].

Plain radiographs of the jaw bone also reveal certain dental changes noted in OFC including the characteristic "ground glass appearance" of the jaw bones caused by extensive demineralization of the medullary bones of the jaw and extensive loss of lamina dura surrounding the roots of the teeth. 

X-Ray Abnormal
  • Mental status changes or psychiatric disorders Unexplained neuromuscular symptoms, constipation, and polyuria Biochemical abnormalities, such as: Elevated alkaline phosphatase, Hypophosphatemia, Hypercalciuria Shortened QT interval on electrocardiogram X-ray[enotes.tripod.com]
Ground Glass Appearance
  • Plain radiographs reveal a characteristic "ground glass appearance". On nuclear imaging, brown tumors could be identified. These are advanced cysts which are lined by osteoclasts and blood pigments.[symptoma.com]

Treatment

Primary hyperparathyroidism is said to be more prevalent than once thought [20]. The high incidence is attributed to the excellent diagnostic tools for serum calcium analysis.

Treatment of OFC involves the treatment of the underlying hyperparathyroidism and long-term correction of the OFC. Primary hyperparathyroidism can be treated by surgical removal of the parathyroid adenoma, after which patients demonstrate sustained remission of the OFC. Recovery of bone density is more marked and faster in cancellous bones, such as bones of the lumbar spine, than in cortical bones such as the forearm bones.

Hydration and regular exercise may also contribute to recovery and remission of OFC [21]. If surgical treatment is not possible, medical care can be aimed at reducing serum calcium levels [22].

Prognosis

OFC is very common in severe cases of primary hyperparathyroidism. However, secondary hyperparathyroidism open link from CRF causes renal osteodystrophy. The complications of OFC include bone fractures, deformities, pain, and complications of hyperparathyoidism.

Etiology

There are two pairs of parathyroid glands in the neck. These glands mainly function by maintaining calcium homeostasis. The activity of the glands is mediated by the hormone they produce, parathyroid hormone.

Osteitis fibrosa cystica is caused by excess parathyroid production of PTH. This hormone stimulates osteoclastic resorption of bone, causing them to become fragile. However, some bones may develop areas of weakening with no calcium deposits at all. This phenomenon is termed osteitis fibrosa.

Before 1950, up to 50% of patients with hyperparathyroidism developed osteitis fibrosa. Currently, however, OFC is rare because of early identification and diagnosis of hyperparathyroidism.

Brown tumor, a bone lesion resulting from hyperparathyroidism (primary or secondary), is a complication of OFC [6]. From current investigations, brown tumor is regarded as a reparative lesion rather than a neoplasm. Brown tumors are pathognomonic of secondary hyperparathyroidism from chronic kidney disease [7]. Secondary hyperparathyroidism open link from chronic kidney disease results in renal osteodystrophy, which has five histopathological forms, osteitis fibrosa being the commonest form occurring in 50% of patients with end-stage renal disease. OFC is characterized by increased number and activity of osteoclasts with a tunnelling pattern of resorption of the trabeculae. Osteomalacia is another form of renal osteodystrophy occurring in 7% of patients with end-stage renal disease [8]. Osteomalacia also occurs as a result of impaired bone mineralization, mainly due to deposition of aluminium at the sites of mineralization.

Epidemiology

There have been notable changes in the epidemiology and pattern of clinical presentation of primary hyperparathyroidism since it was described in 1940 by Fuller Albright. It has been noted in the United Kingdom, United States, and many European countries that the incidence of primary hyperthyroidism has increased since it was described in 1940. It has also been observed among these countries that the pattern of presentation of the disease has altered significantly: In countries with multiple screening techniques, most of the patients with primary hyperparathyroidism are asymptomatic and skeletal and renal complications including OFC are not common. In the East, Middle East, and some countries in the southern hemisphere, the pattern of manifestation has remained unchanged.

A study, conducted to determine the effects of vitamin D and calcium on the occurrence of disease and etiogenesis of a parathyroid tumor in patients with primary hyperparathyroidism, revealed that strengthening of milk by mixing of vitamin D coincided with a reduction in prevalence of OFC and reduced progression of parathyroid tumor in the United States, between 1945 and 1960. In parts of the world where vitamin D deficiency is endemic, however, progression of OFC and development of parathyroid tumor was unaltered.

Generally, Asian Indians are noted to have larger parathyroid tumors than Americans, and black Americans had larger tumors than whites. However, using the serum 25-hydroxyvitamin D level (which is the best index for analyzing vitamin D intake) and parathyroid tumor weight (which best gives information about the growth of the parathyroid tumor), these indices showed no significant difference between whites, Asian Indians, and blacks.

This concludes that vitamin D and calcium nutrition affects both the pattern of disease and growth of the parathyroid tumors in patients with primary hyperparathyroidism. Therefore, it could help if better nutritional policies are executed in developing countries.

Sex distribution
Age distribution

Pathophysiology

Osteitis fibrosa cystica represents the late changes in bone in patients with primary or secondary type of hyperparathyroidism. OFC is characterized by increased bone resorption due to stimulation of osteoclasts by excess parathyroid hormone. Because of the better diagnosis of hyperparathyroidism, OFC is rare.

Histologically, the bone changes in OFC are characterized by proliferation of osteoblasts and accumulation of fibroblasts over the trabecular surfaces and the bone marrow cavity. This cellular proliferation produces peritrabecular fibrosis which is a characteristic of OFC. 

A common form of secondary hyperparathyroidism is renal osteodystrophy. Renal osteodystrophy occurs in chronic renal failure. CRF leads to impaired glomerular filtration and impaired renal vitamin D synthesis, which in turn, cause reduced calcium absorption. Ultimately, a reduction in serum calcium occurs as a sequel to increased serum phosphate levels. This results in stimulation of the parathyroid glands to produce excess PTH to counter the chronic hypocalcemia, leading to in effect an increased serum calcium level.

In renal osteodystrophy, there is bone remodelling which comprises of osteoblast and osteoclastic differentiation [9] [10]. This cycle of events begins with the osteoclastic differentiation resulting in an initial bone resorption. Following this stage of osteoclastic activity, there is increased deposition of calcium and activation of certain factors involved in bone matrix formation [11]. This inhibits the osteoclastic activity and causes the removal of the osteoclasts from the bone surface. Some of these factors include bone morphogenetic proteins [BMP], fibroblast growth factor, and heparin-bound growth factors. These factors are responsible for recruiting osteoblasts and osteoblast precursors into the lacunae formed by the osteoclastic activities [12] [13]. Bone formation results from these osteoblastic activities and consists of matrix formation, bone mineralization, replacement of woven bone with vascularized bone, and osteoblastic proliferation.

This bone remodelling cycle is characterized by an imbalance between the osteoclastic and osteoblastic activities such that more bone is removed than is formed. This causes significant reduction in bone density and strength.

Dialysis-related amyloidosis is another bone lesion which occurs in patients on prolonged dialysis. It results from accumulation and deposition of beta-2 microglobulin. However, the incidence of dialysis-related amyloidosis is reducing because of the current increased use of high-flux dialyzers which have high clearance of beta-2 microglobulin.

Prevention

In general practice, the presence of hyperparathyroidism is first suspected during routine blood tests for other conditions. A high serum calcium may be detected after such routine investigations. Since bone disease is the main cause of death and suffering in patients with hyperparathyroidism, it is recommended that patients with chronic kidney disease open link should have routine serum calcium, phosphate, and PTH tests and these values should be maintained within the normal ranges [23] [24] [25] [26]. Routine X-rays and echocardiography may identify vascular calcifications.

Summary

Osteitis fibrosa cystica is a condition which occurs in long-standing and advanced stages of hyperparathyroidism, either primary or secondary. Osteitis fibrosa cystica is characterized by increased bone turnover. Primary hyperthyroidism is the commonest cause of osteitis fibrosa, occurring in 80-85% of cases [1] [2]. Most cases of secondary hyperparathyroidism which result in osteitis fibrosa are due to chronic renal failure (CRF). Parathyroid adenomas constitute the commonest cause of primary hyper parathyroidism in osteitis fibrosa cystica.

The two pairs of parathyroid glands synthesize and secrete the parathyroid hormone (PTH) which is crucial for calcium and vitamin D homeostasis. PTH acts by increasing the renal tubular reabsorption of calcium, intestinal absorption of calcium, and renal synthesis of vitamin D. In excessive parathyroid activity, there is calcium build up in the blood which may trigger the bone remodelling and other changes featured in osteitis fibrosa cystica.

Osteitis fibrosa cystica presents with bone weakness, bone pain, and bone fractures. Generally, the clinical features which manifest are a reflection of hypercalcemia and loss of bone density. Hypercalcemia predisposes to kidney stones [3]. Other symptoms include nausea, loss of appetite, and weight loss.

Osteitis fibrosa cystica is rare compared to its incidence many decades ago, because of better and earlier diagnosis of hyperparathyroidism which is often made during routine blood calcium tests. It is commoner among women than men and it is generally most commonly seen in individuals between the ages of 50 and 60. In cases where it occurs in much younger patients, multiple endocrine neoplasia types I and II should be excluded [4].

Diagnosis of osteitis fibrosa cystica is made by laboratory blood investigations to assess the serum levels of calcium, parathyroid hormone, and alkaline phosphatase. Imaging studies, particularly plain radiographs, are necessary in the diagnosis of osteitis fibrosa cystica. Plain radiographs reveal a characteristic "ground glass appearance". On nuclear imaging, brown tumors could be identified [5]. These are advanced cysts which are lined by osteoclasts and blood pigments.

Treatment of osteitis fibrosa and hyperparathyroidism is by parathyroidectomy or conservative management which involves lowering serum calcium and monitoring serum calcium and PTH levels.

Patient Information

Osteitis Fibrosa Cystica (OFC) is a term which describes the bone changes which occur as a result of a condition called hyperparathyroidism. There are two pairs of parathyroid glands located behind the thyroid gland at the back of the neck. These glands produce a hormone called parathyroid hormone which helps to regulate the levels of calcium, vitamin D, and phosphorus in the body.

When these glands work excessively as a result of some intrinsic diseases such as tumors, it is referred to as primary hyperparathyroidism. However, if the overactivity of the parathyroid glands results from a disease of another organ, it is called secondary hyperparathyroidism.

Parathyroid hormone functions to increase the level of calcium in the blood when it falls. It serves three functions:

  • Increasing calcium reabsorption from the kidneys
  • Causing absorption of calcium from the intestine
  • Increasing the production of vitamin D in the body. Vitamin D helps in the absorption of calcium by the intestinal cells.

Excess activity of the parathyroid glands is called hyperparathyroidism, which is responsible for osteitis fibrosa cystica. Excess parathyroid hormone causes increased breakdown of the bones and eventually making them weak and fragile.

Before 1950, almost half of the total number of patients with hyperparathyroidism had osteitis fibrosa cystica. Currently, the incidence has reduced mainly because hyperparathyroidism can be detected earlier before the bone complications arise.

  • Hyperparathyroidism open link presents with several features including fatigue, constipation, and urinary frequency.
  • Osteitis fibrosa cystica also presents with some common features, including bone pain, weakness, and may eventually predispose the bones to fracture and deformities.
  • The bone changes in osteitis fibrosa cystica are commonly seen in the jaw, skull bones, spine, and bones of the fingers and toes.

The diagnosis of osteitis fibrosa cystica involves certain laboratory blood tests to check for the levels of calcium, phosphate, and the parathyroid hormone. X-rays are also necessary to reveal the characteristic bony changes associated with the disease. X-rays of the jaw are also necessary.

Treatment of osteitis fibrosa cystica can be achieved by surgical removal of the overactive parathyroid glands, a procedure called parathyroidectomy. In cases where surgery is not possible, drugs may be administered to reduce the level of calcium in the blood ****.

References

Article

  1. Bilezikian JP. Primary Hyperparathyroidism, 2011, http://www.endotext.org/parathyroid/parathyroid5/parathyroidframe5.htm.
  2. Kearns AE. Thompson GB. Medical and surgical management of hyperparathyroidism. Mayo Clinic Proceedings. 2002;77 (1): 87–91.
  3. Murray JF, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Raven Press, New York, USA, 2nd edition; 1993.
  4. Marx SJ. Hyperparathyroid genes: sequences reveal answers and questions. Endocrine Practice. 2011;17 (supplement 3):18–27.
  5. Rubin MR, Livolsi VA, Bandeira F, Caldas G, Bilezikian JP. Clinical case seminar: Tc99m-sestamibi uptake in osteitis fibrosa cystica simulating metastatic bone disease. Journal of Clinical Endocrinology and Metabolism.2001; 86(11): 5138–5141.
  6. Soundarya N, Sharada P, Prakash N, Pradeep G. Bilateral maxillary brown tumors in a patient with primary hyperparathyroidism: Report of a rare entity and review of literature. J Oral Maxillofac Pathol. 2011;15:56–9. 
  7. Fineman I, Johnson JP, Di-Patre PL, Sandhu H. Chronic renal failure causing brown tumors and myelopathy. Case report and review of pathophysiology and treatment. J Neurosurg. 1999;90:242–6. 
  8. Hutchison A.J., R.W. Whitehouse, H.F., Boulton, et al. Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. Kidney Int. 1993; 44:1071-1077
  9. Rodan GA. Bone homeostasis. Proc Natl Acad Sci USA. 1998; 95:13361–13362
  10. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell.1997; 89:747–754.
  11. Miyauchi A, Hruska KA, Greenfield EM, et al. Osteoclast cytosolic calcium, regulated by voltage operated calcium channels and extracellular calcium, controls podosome assembly and bone resorption. J Cell Biol.1990; 111:2543–2552
  12. Yoneda T. Cytokines in bone: local translators in cellto-cell communications. In: Peck WA (ed) Cellular and molecular biology of bone. Academic Press, San Diego. 1993; 375–412.
  13. Auclair PL, Avendt DM, Hellstein JW. Giant cell lesions of the jaws. Oral Maxillofac Surg Clin North Am. 1997;9:655–80.
  14. Som PM, Lawson W, Cohen BA. Giant-cell lesions of the facial bones. Radiology. 1983;147:129–34.
  15. Kaugars GE, Niamtu J, 3rd, Svirsky JA. Cherubism: Diagnosis, treatment and comparison with central giant cell granulomas and giant cell tumors. Oral Surg Oral Med Oral Pathol. 1992;73:369–74.
  16. Langlias RP, Langland OE, Nortje CJ. Diagnostic imaging of the jaws. In: Cooke D, Zinner S, DiRienzi D, eds. Generalized Rarefactions. 1st ed. Baltimore: Williams and Wilkins; 1995: 63–4.
  17. Muntner P, Jones TM, Hyre AD, et al. Association of serum intact parathyroid hormone with lower estimated glomerular filtration rate. Clin J Am Soc Nephrol. 2009;4:186–194. 
  18. Krause I, Eisenstein B, Davidovits M, Cleper R, Tobar A, Calderon S. Maxillomandibular brown tumor-a rare complication of chronic renal failure. Pediatr Nephrol. 2000;14:499–501. 
  19. Prado FO, Rosales AC, Rodrigues CI, Coletta RD, Lopes MA. Brown tumor of the mandible associated with secondary hyperparathyroidism: A case report and review of the literature. Gen Dent. 2006; 54:341–3.
  20. Maina AM, Kraus H. Case Report Successful Treatment of Osteitis Fibrosa Cystica from Primary Hyperparathyroidism. Case Reports in Orthopedics. Volume 2012 (2012), Article ID 145760, 3 pages. http://dx.doi.org/10.1155/2012/145760. Accessed, October 23, 2015. 
  21. Rubin MR, Livolsi VA, Bandeira F, Caldas G, Bilezikian JP. Clinical case seminar: Tc99m-sestamibi uptake in osteitis fibrosa cystica simulating metastatic bone disease. Journal of Clinical Endocrinology and Metabolism. 2001; 86 (11): 5138–5141.
  22. Agarwal G, Mishra SK, Kar DK, Singh AK, Arya V, Gupta SK, Mithal A. Recovery pattern of patients with osteitis fibrosa cystica in primary hyperparathyroidism after successful parathyroidectomy. Surgery. 2002; 132(6):1075-83.
  23. Muntner P, Jones TM, Hyre AD, et al. Association of serum intact parathyroid hormone with lower estimated glomerular filtration rate. Clin J Am Soc Nephrol. 2009;4:186–194.
  24. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1–S201.
  25. KDIGO CKD-MBDWork Group. KDIGO clinical practice guidelines for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 2009;76: S1–S130.
  26. London GM, Guérin AP, Marchais SJ, et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18:1731–1740.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2018-06-21 22:54