Ribbing disease is a rare bone dysplasia characterized by thickening of the diaphysis of the long bones of the lower extremities in young adults. Patients with Ribbing disease typically present with pain in one tibia, but the disease often sequentially involves both tibiae and both femora. It is often initially diagnosed as low-grade osteomyelitis, but it may also be confused with other causes of increased bone density. The level of pain is variable and may be severe.
A thirty-two-year-old woman presented with a three and a half-year history of pain in the lower extremities. The onset of pain had been in the left tibia. Initial radiographs demonstrated increased diaphyseal density and thickness, and a technetium bone scan demonstrated increased uptake. The white blood-cell count was normal. Low-grade osteomyelitis was suspected. The tibia was biopsied and cultures were performed on two occasions, without bacterial growth. The patient was treated empirically with antibiotics, but the symptoms did not resolve. Pain subsequently developed in the right tibia and femur. The patient consulted multiple physicians, who treated her with vitamins, antibiotics, ibuprofen, and alendronate, with no effect on the pain.
At presentation, the greatest pain was in the right thigh. The pain was constant, deep, aching, throbbing, variable in intensity, and worse at night, preventing sleep. The pain was worsened by physical activity and somewhat decreased by rest and hot baths. It was not relieved by tramadol or hydrocodone.
On physical examination, the patient was found to be of normal height, weight, and proportion with no deformity, contracture, or muscle weakness. The skin temperature over both tibiae was increased, but the thigh temperature was normal.
Laboratory evaluation demonstrated a normal white blood-cell count, hemoglobin level, and sedimentation rate. The serum electrolyte levels and liver function tests were normal, although the alkaline phosphatase level was at the upper limit of normal on three occasions. Bone-specific alkaline phosphatase was 14.4 µg/L (normal, 2.9 to 20 µg/L).
A review of the initial radiographs demonstrated eccentric sclerosis with both endosteal and periosteal thickening of the midpart of the left tibial diaphysis ( Fig. 1 ). There was subtle sclerosis with endosteal cortical thickening of the midpart of the right tibia. The right femur had mild, nonuniform endosteal sclerosis and cortical thickening of the proximal and midparts of the shaft. The left femur was normal. Technetium bone scans showed increased skeletal uptake corresponding to the abnormal densities of the right femur and both tibiae, with no increase in uptake in the left femur or other bones. A gallium scan revealed minimal uptake, indicating a low probability of infection. A computed tomography scan demonstrated endosteal thickening of the midparts of the right femur and right tibia and extensive endosteal and periosteal thickening of the left tibia ( Fig. 2 ).
Histologic examination of the tibial cortical biopsy specimens ( Fig. 3 ) revealed osteosclerosis and foci of woven bone. Dense lamellar bone and normal cortical bone melded without sharp demarcation. The number of haversian canals was increased, and although some were of normal caliber many were markedly decreased in diameter. Circumferential lamellae associated with the haversian canals appeared unevenly spaced, poorly defined, and irregular. Increased numbers of osteocytes per unit of bone were present. No increase in osteoblasts or osteoclasts was seen.
Radiographs made three and a half years after the onset of symptoms and the biopsy showed progression of endosteal and periosteal thickening of each tibial diaphysis. The midportion of the medullary canal was almost obliterated in both tibiae ( Figs. 4 and 5 ). There was endosteal and periosteal sclerosis of the right and left femoral shafts with focal narrowing of the medullary canal in the left femoral shaft ( Fig. 6 ).
Magnetic resonance imaging demonstrated cortical thickening and narrowing of the canal with decreased signal on both T1-weighted and STIR (short tau inversion recovery) images, characteristic of cortical bone. Variable areas of nonspecific marrow edema and periosteal edema were seen with gadolinium enhancement.
In an effort to relieve pain, intramedullary reaming of the right femur was performed because it was the most symptomatic bone. The rationale for the surgery was based on the formulation by Rubin that indicated that sclerotic bone produces pain because the intraosseous vessels lack room for expansion in the dense bone 1 . Following entry into the femur, bone fragments were obtained from the diaphyseal endosteal surface with use of a cement-removal instrument prior to reaming. The canal was reamed to 13 mm. The femoral pain, which the patient rated as 9 on a visual analog scale of 0 to 10 preoperatively, was rated as 0 following the surgery.
Histologic examination of the intramedullary tissue ( Fig. 7 ) revealed nonspecific reactive changes consisting of thickened trabeculae composed of lamellar bone and foci of woven bone with prominent osteoblasts and scant fibrosis.
Progressive, severe pain subsequently developed in the right tibia, in association with near obliteration of the medullary canal. The patient was treated with intramedullary reaming of the tibia. The tibial cortex was perforated during the reaming because of difficulty with locating the canal. The tibia was therefore protected in a non-weight-bearing cast for six weeks. The pain in the right tibia resolved completely. At the time of the latest follow-up, at three years, the right femur and tibia were pain-free and the medullary canals were patent. The pain in the left femur and tibia had increased, in association with increased endosteal ossification, and at the time of writing was being treated with nonsteroidal anti-inflammatory medication. The patient continued to work in a sedentary job.
The condition observed in our patient was described by Ribbing in 1949 2 . He reported diaphyseal involvement of the tibia and other long bones in four of six siblings. Several cases have been subsequently described, with use of various names for the condition 3-7 , although one of the cases reported by Seeger et al. may represent intramedullary sclerosis 7 . As described by Abdul-Karim et al. 8 , intramedullary sclerosis is characterized by a unilateral increase in endosteal bone density without cortical thickening. It is associated with increased uptake on bone-scanning, and symptoms are decreased by excision of the dense bone 8 . There have been additional reports that are difficult to evaluate. The patients in the report by D'Addabbo et al. may have had Ribbing disease, but the cases are incompletely described 9 . Iwasaki et al. described a patient with amyotrophic lateral sclerosis who had unilateral endosteal hyperostosis of the tibia and a negative bone scan 10 . A cousin of the patient, who was not affected by amyotrophic lateral sclerosis, had unilateral increased tibial diaphyseal density associated with cortical enlargement. These patients probably did not have Ribbing disease.
Our review of twelve cases reported prior to the study by Seeger et al. 7 revealed that seven females and five males with an average age at onset of twenty-three years had Ribbing disease. Bone pain was present in nine of the twelve patients. The series reported on by Seeger et al. included six patients, all female, with a mean age of forty-one years. The total group of eighteen patients consisted of thirteen women and five men with an average age of thirty years. The tibia was involved in fifteen patients, and twelve had bilateral tibial involvement. The femur was affected in seven patients, and five had bilateral femoral involvement. There were two reports of involvement of the fibula and radius and one report of involvement of the ulna. All patients who had technetium bone-scanning had increased uptake. Ten of the eighteen patients had a biopsy, and no organisms grew on culture of any of the biopsy specimens except for one from a patient in the report by Seeger et al. Staphylococcus epidermidis grew on culture of that specimen and was thought to be a contaminant. A distinctive feature of Ribbing disease is asynchronous involvement. The interval between the development of symptoms in one tibia and the development of symptoms in the contralateral tibia, in the seven patients for whom such data were available, ranged from nine months to ninety-six months and averaged thirty-six months. The families studied by Ribbing 2 and by Paul 3 and one of the patients of Seeger et al. had affected siblings, suggesting the possibility of recessive inheritance, although environmental causes cannot be ruled out.
The distinctive radiographic finding is fusiform, nearly circumferential, cortical thickening associated with endosteal sclerosis of the diaphysis, with sparing of the epiphyseal and metaphyseal areas. Involvement is usually limited to the tibiae and femora 6,7 . Both endosteal and periosteal new-bone formation is clearly shown by computed tomography. Disease progression is manifested by longitudinal spread along the diaphysis and obliteration of the medullary canal.
The histopathologic findings most frequently described in patients with Ribbing disease are cortical osteosclerosis with formation of dense periosteal and endosteal new bone and narrowed haversian canals 2,6,11,12 . Other reported features include periosteal inflammation, increased numbers of osteocytes per unit of bone, focal increased osteoblastic activity, and absence of evidence of active bone resorption. These findings are not sufficiently distinctive to permit a diagnosis of Ribbing disease on the basis of bone morphology alone. Biopsy does allow the exclusion of other diagnoses.
Ribbing 2 and others 6 have indicated that the radiographic findings stabilize and symptoms spontaneously decrease with time but improvement is slow and incomplete. One additional affected patient seen at our institution had a spontaneous decrease in pain but continued to use daily nonsteroidal analgesics at the time of writing. There is limited information regarding the effect of biopsy on pain in patients with this dysplasia. The case reported by Fallon et al. included curettage of the canal, and this resulted in immediate pain relief 4 . Following intramedullary reaming, our patient had dramatic pain relief in both the femur and the tibia. Removal of sclerotic endosteal bone by intramedullary reaming may explain this pain relief, but there may be alternative explanations. Pain is not universal; asymptomatic patients have been described, and some patients have pain at only one of several affected bones.
The differential diagnosis of unilateral increased density and thickness of the tibia includes osteoid osteoma, stress fracture, adamantinoma, fibrous dysplasia, osteosarcoma, melorheostosis, hyperphosphatasia, histiocytosis, lymphoma, intramedullary sclerosis, osteomyelitis, and Ribbing disease. Bilateral increased density and thickness of the tibia may be associated with bone dysplasias such as Van Buchem and Worth endosteal hyperostosis, sclerosteosis, Camurati-Engelmann disease, and Ribbing disease.
The bone dysplasia most likely to be confused with Ribbing disease is Camurati-Engelmann disease 12,13 . Camurati-Engelmann dysplasia is transmitted by dominant inheritance, and the causative gene is on chromosome 19q13 14 . Some authors have considered these conditions to be the same disease. However, although they have in common endosteal involvement of the diaphysis of long bones, variable severity, and progression of the disease, these conditions are differentiated by several important features. Radiographically, the diaphyseal involvement in Ribbing disease is central with respect to the longitudinal axis of the tubular bone, whereas in Camurati-Engelmann disease it is eccentric and farther away from the faster growing epiphysis. Ribbing disease may become static, but Camurati-Engelmann disease is progressive. The involvement in Camurati-Engelmann disease is bilateral and symmetric, whereas Ribbing disease usually presents unilaterally or asymmetrically with asynchronous, bilateral involvement 13 . Additional features of Camurati-Engelmann disease are metaphyseal involvement leading to an Erlenmeyer flask and valgus deformity of the femur. Camurati-Engelmann disease may also involve the skull, mandible, vertebrae, upper extremities, metatarsals, and metacarpals 12,13 . These findings are absent in Ribbing disease ( Table I ).
In summary, Ribbing disease is a distinct and rare bone dysplasia. When Ribbing disease is suspected, a bone scan should be performed to ascertain the extent of involvement. Siblings of affected individuals should be evaluated for the presence of the disease to clarify its inheritance. The ominous nature of the differential diagnosis suggests that biopsy is usually indicated. Severe pain may be relieved by intramedullary reaming of the affected long bones.