Incidence of brachydactyly and hand exostosis in hereditary multiple exostosis

Forty-two radiographs and charts of twenty-two patients with a diagnosis of hereditary multiple exostosis and hand involvement were examined to determine the incidence of hand exostoses and association with brachydactyly. An average of 11.6 exostoses were found per hand. The proximal phalanges and metacarpals are affected in the majority of patients and the thumb and distal phalanges are rarely involved. Most exostoses were located in the juxtaepiphyseal region (61.8%) and typically involved less than 50% of the bone diameter. Brachydactyly can be seen in patients with hereditary multiple exostosis when no exostoses is present; however, the presence of an exostosis results in even more shortening. The location and size of the exostosis had no relationship to increased bone shortening. Operative treatment was required in four of twenty-two patients for debulking and impingement.     

Cervical myelopathy in hereditary multiple exostoses

Spinal cord compression due to cervical exostoses is a rare but recognized complication of hereditary multiple exostosis (HME), an autosomal dominant disorder. This disease, also called multiple osteochondromatosis, is characterised by osteocartilaginous exostoses, typically involving the juxtaepiphyseal regions of long bones. Complications such as transformation to sarcoma (1 to 5%) or neurological compression (of the spinal cord, 1 to 9%) can arise during the course of the disease. We report the case of a 64-year-old man with progressive difficulties in walking over many years, ascribed to congenital rachitism. A diagnosis of HME was not made until late in the disease course. Investigations revealed cervical myelopathy due to vertebral exostosis as well as multiple exostoses in other sites. His gait was not improved after surgical decompression. A better knowledge of this disease could have prevented this neurological complication.     

Distinct chromosomal rearrangements in subungual (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation (Nora lesion)

BACKGROUND: Proliferative lesions of the bone surface, such as subungual (Dupuytren) exostosis and bizarre parosteal osteochondromatous proliferation (BPOP, Nora lesion) are currently classified as reactive, proliferative processes that mimic primary neoplasms of bone. METHODS: Cytogenetic analysis was performed on 3 subungual exostoses of the great toe and 2 BPOP lesions of the radius and ulna. RESULTS: A balanced translocation t(X;6) was identified in all cases of subungual exostoses. The chromosomal rearrangements observed in 1 case of BPOP differed from those seen in subungual exostosis. CONCLUSIONS: The presence of chromosomal abnormalities in subungual exostosis and BPOP suggests that these lesions are neoplastic, with a different molecular pathogenesis, and that each is a distinct clinicopathologic entity.     

Manifestations of hereditary multiple exostoses

The solitary osteochondroma, a common pediatric bone tumor, is a cartilage-capped exostosis. Hereditary multiple exostosis is an autosomal dominant disorder manifested by the presence of multiple osteochondromas. Linkage analysis has implicated mutations in the EXT gene family, resulting in an error in the regulation of normal chondrocyte proliferation and maturation that leads to abnormal bone growth. Although exostoses are benign lesions, they are often associated with characteristic progressive skeletal deformities and may cause clinical symptoms. The most common deformities include short stature, limb-length discrepancies, valgus deformities of the knee and ankle, asymmetry of the pectoral and pelvic girdles, bowing of the radius with ulnar deviation of the wrist, and subluxation of the radiocapitellar joint. For certain deformities, surgery can prevent progression and provide correction. Patients with hereditary multiple exostosis have a slight risk of sarcomatous transformation of the cartilaginous portion of the exostosis.     

Heparan sulfate abnormalities in exostosis growth plates

Hereditary multiple exostoses (HME), a condition associated with development and growth of bony exostoses at the ends of the long bones, is caused by germline mutations in the EXT genes. EXT1 and EXT2 function as glycosyltransferases that participate in the biosynthesis of heparan sulfate (HS) to modify proteoglycans. HS proteoglycans, synthesized by chondrocytes and secreted to the extracellular matrix of the growth plate, play critical roles in growth plate signaling and remodeling. As part of studies to delineate the mechanism(s) by which an exostosis develops, we have systematically evaluated four growth plates from two HME and two solitary exostoses. Mutational events were correlated with the presence/absence and distribution of HS and the normally abundant proteoglycan, perlecan (PLN). DNA from the HME exostoses demonstrated heterozygous germline EXT1 or EXT2 mutations, and DNA from one solitary exostosis demonstrated a somatic EXT1 mutation. No loss of heterozygosity was observed in any of these samples. The chondrocyte zones of four exostosis growth plates showed absence of HS, as well as diminished and abnormal distribution of PLN. These results indicate that, although multiple mutational events do not occur in the EXT1 or EXT2 genes, a complete loss of HS was found in the exostosis growth plates. This functional knockout of the exostosis chondrocytes' ability to synthesize HS chains further supports the observations of cytoskeletal abnormalities and chondrocyte disorganization associated with abnormal cell signaling.     

Correlative radiographic, scintigraphic, and histological evaluation of exostoses

We reviewed the cases of twenty-four patients with solitary or multiple exostoses to correlate their radiographic, scintigraphic, and histological evaluations. We studied twenty-five excised lesions, two of them exostotic chondrosarcomas, from twenty-two patients. There were two patterns of bone-scan activity and there was a direct correlation between enchondral bone formation and radionuclide uptake in all patients, both skeletally immature and mature. So-called quiescent lesions--those with inactive scans--were those that lacked histological evidence of enchondral bone formation. Those with increased uptake--active exostoses--all demonstrated active formation of enchondral bone. Evidence of active exostotic growth could be demonstrated on bone scans well beyond the time of skeletal maturity. The bone scan did not qualitatively differentiate the benign active exostoses from the two lesions with malignant degeneration. Increased uptake related to enchondral bone formation was a feature of both. An inactive scan, however, seemed to exclude the possibility of malignant degeneration in the exostosis.     

A case of pneumothorax in a patient with costal exostosis

A 21-year-old male was admitted to our hospital complaining of chest pain. He had undergone operations on multiple exostoses of his lower extremities when he was thirteen and fifteen years old. Family history revealed multiple exostoses in his mother and one of his cousins. Chest roentgenograms showed right pneumothorax and a mass arising from the seventh rib in the right lower lung filed. Chest CT revealed that the mass was located in thorax but outside the lung. These findings suggested that the pneumothorax was secondary to the injury of the right lung caused by an exostosis arising from the rib. Upon operation, we found a laceration of the lower lobe and a hard mass the size of a pea protruding from the seventh rib. A small bony spicule was also found to be projecting from the sixth rib. The hard mass and the spicule were resected with a normal portion of the seventh and the sixth ribs. The pathological findings of these bony lesion proved to be consistent with exostosis. The patient's postoperative course was uneventful. This case of pneumothorax caused by an exostosis lacerating the lung is rare.     

Thoracic vertebral body exostosis as a cause of myelopathy in a patient with hereditary multiple exostoses

The posterior thoracic vertebral body appears to be a novel origin for an exostosis causing myelopathy. A patient with hereditary multiple exostoses and myelopathy caused by an exostosis originating from the posterior aspect of the T5 vertebral body was treated with a staged anterior decompression/corpectomy and posterior spinal fusion. The patient had near-complete resolution of his myelopathy immediately after undergoing removal of the exostosis through a right-sided lateral thoracotomy approach. This was a unique origin for an exostosis causing spinal cord compression in a patient with hereditary multiple exostoses. The delivery of the exostosis was performed en bloc during the anterior decompression and corpectomy portion of the surgery. This resulted in the expected favorable outcome.     

EXT 1 gene mutation induces chondrocyte cytoskeletal abnormalities and defective collagen expression in the exostoses.

Hereditary multiple exostoses (HME), an autosomal skeletal disorder characterized by cartilage-capped excrescences, has been ascribed to mutations in EXT 1 and EXT 2, two tumor suppressor-related genes encoding glycosyltransferases involved in the heparan sulfate proteoglycan (HSPG) biosynthesis. Taking advantage of the availability of three different exostoses from a patient with HME harboring a premature termination codon in the EXT 1 gene, morphological, immunologic, and biochemical analyses of the samples were carried out. The cartilaginous exostosis, when compared with control cartilage, exhibited alterations in the distribution and morphology of chondrocytes with abundant bundles of actin filaments indicative of cytoskeletal defects. Chondrocytes in the exostosis were surrounded by an extracellular matrix containing abnormally high amounts of collagen type X. The unexpected presence of collagen type I unevenly distributed in the cartilage matrix further suggested that some of the hypertrophic chondrocytes detected in the cartilaginous caps of the exostoses underwent accelerated differentiation. The two mineralized exostoses presented lamellar bone arrangement undergoing intense remodeling as evidenced by the presence of numerous reversal lines. The increased electrophoretic mobility of chondroitin sulfate and dermatan sulfate proteoglycans (PGs) extracted from the two bony exostoses was ascribed to an absence of the decorin core protein. Altogether, these data indicate that EXT mutations might induce a defective endochondral ossification process in exostoses by altering actin distribution and chondrocyte differentiation and by promoting primary calcification through decorin removal.     

Disturbed growth in height in multiple cartilaginous exostoses (author's transl)]

Basing on the hypothesis that reduced body height in patients with multiple cartilaginous exostoses would be mainly accounted for by shorter extremities, not by a shorter trunk, the authors clinically examined 19 exostosis patients in respect of thigh, lower leg, upper and lower arm, as well as height of the seated patient. The dimensions were compared by the method of matched pairs, with 19 volunteers without diseased skeleton, who corresponded with one of the exostosis patients in respect of age, sex and height of seated patient. Results were evaluated according to Wilcoxon's test. This showed a statistically significant reduction in length of the extremities in adults with multiple cartilaginous exostoses.     

Variance of radial growth in vascularized and nonvascularized free bone grafts including epiphysis in puppies

A portion of radius including the proximal epiphysis was either transplanted or excised and replaced in puppies. In these growing animals, growth in long bone grafts vascularized by periosteal and endosteal vessels but not epiphyseal vessels, was significantly greater than in nonvascularized grafts, but was less than normal growth (63 percent to 67 percent of normal). In nonvascularized grafts, the epiphyses closed one month postoperatively, while they closed at five months in vascularized grafts and at six months in normal controls. This study confirms that approximately two-thirds of normal longitudinal bone growth can be accomplished with a bone transplant that includes a vascular pedicle supplying the endosteum and periosteum, but not the physis.     

Rare case of popliteal artery injury caused by distal femoral exostosis. Case report

Complications of multiple exostoses occur rarely and articles about it can be found occasionally. We found reasonable to report our case because of its rarity. A female patient of 17 was under treatment in the Orthopaedic Clinic with multiple exostoses. Before her admission to the Clinic, a suddenly, painful swelling in the distal-third of the left femur occurred, and then a well detailed examination has done (bone radiograph, angiogramm, MR). The examinations arised the presence of pseudoaneurysm as a background of the swelling of the soft tissue, as well as the possibility of juvenile bone tumor at the same time. During the operation we detected a sharp exostosis on the distal medial condyle of the femur, which occurred a lesion on the popliteal artery. It was the base of forming the pseudoaneurysm. As a conclusion we would like to underline that during the attend of such cases, the presence of vascular surgical team is necessary.     

Spinal cord compression due to vertebral osteochondroma: report of two cases

Osteochondroma, or exostosis, is the most common of all benign bone tumors. Spinal osteochondromas are uncommon but may cause neurological compromise. We report two cases of spinal cord compression by osteochondromas. One patient was a 17-year-old man with hereditary multiple exostoses who was presented with spastic paraparesis, a sensory level at T3-T4, and a pyramidal syndrome. Vertebral exostosis was suspected by magnetic resonance imaging and confirmed by histological examination. Surgical decompression was followed by complete resolution of the neurological impairments. The other patient was a 19-year-old man with spastic paralysis of the right lower limb and a pyramidal syndrome. Whereas magnetic resonance imaging suggested a neurofibroma, histological features were those of osteochondroma. Nine months elapsed from symptom onset to surgery. This delay led to residual neurological impairments, which resolved almost completely after rehabilitation therapy. Vertebral osteochondromas contribute only 1.3-4.1% of all osteochondromas. The lesion may be solitary or a manifestation of hereditary multiple exostosis. Magnetic resonance imaging shows the exact location of the lesion, most notably with relation to neighboring neurological structures. Spinal cord compression is uncommon and usually has a favorable outcome provided surgical decompression is performed before major neurological damage develops.     

The Taniguchi classification in cases of multiple cartilaginous exostoses]

27 patients treated surgically at Child Orthopaedic Clinic of Pomeranian Medical Academy between 1974-1996 for multiple cartilaginous exostosis (Aclasia Diaphysealis Keith) were classified into three groups according to the Taniguchi classification. This classification is based on whether multiple cartilaginous exostoses are present on distal forearm. Group I--no involvement of the distal forearm (n = 2), in group II involvement of the distal forearm without shortening of either bone (n = 7) was stated. Group III consists of members with involvement of the distal forearm with shortening the radius or the ulna (n = 18). Groups were compared with regard to: number of lesions, distribution of exostoses in different body areas, age of onset of the Keith disease, height of children, presence of valgus deformity of the ankle, dislocation of the radial head and presence of exostoses around hip area. This classification should be useful in estimating severity of Keith disease, identifying cases at high risk for complications like dislocation of the radial and malignant transformation.     

Reconstruction of forearm deformities in multiple cartilaginous exostoses

The management of complex forearm deformities in patients with multiple cartilaginous exostoses is controversial. The objective of this study is to look into the outcome of treatment with the combined use of ulna lengthening, radial osteotomy, and excision of exostosis in our six patients, who all had Masada type 1 deformity of the forearm. Clinical assessment was performed using the pre- and postoperative range of motion of the wrist, forearm and elbow. The chief symptom each patient had was noted as well as the demographic data of all patients. Radiological assessment was performed by checking the degree of negative ulna variance, the radial articular angle, and the degree of carpal slip. The degree of satisfaction of the patients and their parents were noted. Good clinical and radiological results were obtained at a mean follow-up of 2.5 years. All patients and parents were satisfied and there was no recurrence of deformity in the latest follow-up. The authors believe in early and aggressive treatment of Masada type 1 deformity of the wrist and forearm for multiple cartilaginous exostoses with a combination of excision of exostosis, ulna lengthening and radial osteotomy.     

Subungual exostoses.

From 1910 through 1975, forty-four patients with subungual exostoses were seen at the Mayo Clinic. Thirty-four of them had the exostosis on the great toe. Forty-three of the patients were treated by local excision and one was treated by amputation of the hallux. Five patients had local recurrence. None of the tumors underwent malignant change. Histologically, the tumors consisted of a proliferating fibrocartilaginous gap that merged into mature trabecular bone at its base. The growth in the cap was so active that is sometimes mimicked sarcoma, but no true anaplasia was seen. The subungual exostoses were uniformly benign, and local excision was the treatment of choice.     

Popliteal false aneurysm complicating osteochondroma. A case report.

A false aneurysm of the popliteal artery, caused by an exostosis in a patient with multiple exostoses, is described.     

Canine prostate induces new bone formation in mouse calvaria: A model of osteoinduction by prostate tissue

BACKGROUND: Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites may also lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor-cell osteoinduction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue. METHODS: Collagenase-digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post-implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate-resistant acid phosphatase staining for osteoclasts. RESULTS: The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate-implanted calvaria significantly increased (1.7-fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically-induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue. CONCLUSIONS: This animal model will be useful for investigating the roles of prostate-derived growth factors on new bone formation in vivo.     

Physeal fractures,part II: fate of interposed periosteum in a physeal fracture

This study describes the histologic features of periosteum interposed into a physeal fracture of the rat proximal tibia. Periosteum was introduced into a physeal fracture in two groups of animals: those with an intact physis after fracture, and those with the medial half of the physis surgically ablated. Specimens of the proximal tibia underwent histologic analysis at 2, 4, 6, 10, and 21 days after fracture to determine the histologic features of interposed periosteum in a physeal fracture. In animals with an intact physis, interposed periosteum underwent one of two fates: it was degraded by giant cells in the fracture plane, which allowed cellular infiltration, or if the periosteum was closely surrounded by physeal cartilage, the physis grew around it and appeared to force it toward the metaphysis. In animals whose physis received surgical ablation, physeal bar formation was always present, with poor organization of the remaining lateral growth plate. Histologic evidence from this study also underscores the fact that physeal bar formation occurs from the migration of osteoblasts and osteoclasts along vertical septa.     

Intra-acetabular localisation of an osteochondroma causing subluxation of the hip joint

INTRODUCTION: Intra-acetabular localisation of an osteochondroma causing subluxation of the hip joint is a rare entity in children suffering from multiple hereditary exostoses. In literature only 6 operatively treated cases have been reported. CASE: We add the case of an 8-year-old boy with an intraarticular exostosis of the left acetabulum causing subluxation of the hip. Using an anterolateral approach to the hip joint this exostosis was removed surgically together with some extraarticular exostoses of the proximal femur. The hip could be re-centered in combination with an additional varus derotation osteotomy of the proximal femur. Intraoperatively the femoral head was only subluxated to minimise the risk of avascular necrosis. After a follow-up of two years the patient has complete remission of symptoms and there is no evidence of avascular necrosis radiologically with good remodelling of the left hip. CONCLUSION: The operative treatment of an intraarticular exostosis of the hip joint is a difficult and risky surgical procedure. The reported open surgical procedure allowed resection of the intraarticular exostosis in combination with therapy of additional pathologies of the proximal femur.