[Ribbing disease: apropos of a case]. / Enfermedad de Ribbing: a propósito de un caso.

Ribbing's disease is a rare form of sclerosing bone dysplasia characterized by exuberant yet benign endosteal bone, and periosteum formation in the diaphysis of long bones. Diagnosis relies on exclusionary criteria, as the primary clinical manifestations entail progressive pain unresponsive to analgesic therapy, accompanied by serological markers within normal ranges. Pain management constitutes the cornerstone of treatment, with surgery appearing to offer the most efficacious approach, despite the absence of a standardized therapeutic algorithm. The diagnostic and therapeutic delays associated with Ribbing's disease, reaching up to 16 years, exert a profound impact on patients' quality of life. Hence, the purpose of our work is to present a case report of Ribbing's disease and conduct a comprehensive literature review on the subject matter.

La enfermedad de Ribbing es una forma rara de displasia ósea esclerosante caracterizada por una formación exuberante, aunque benigna, de hueso endóstico y periostio en la diáfisis de los huesos largos. El diagnóstico se basa en criterios de exclusión, ya que las manifestaciones clínicas principales implican dolor progresivo que no responde a analgésicos, acompañado de marcadores serológicos normales. El manejo del dolor constituye la piedra angular del tratamiento y la cirugía parece ofrecer el enfoque más efectivo, a pesar de no contar con un algoritmo terapéutico estandarizado. Los retrasos diagnósticos y terapéuticos asociados con la enfermedad de Ribbing, que pueden alcanzar hasta 16 años, impactan profundamente en la calidad de vida de los pacientes. Por lo tanto, el propósito de nuestro trabajo es presentar un reporte de caso de la enfermedad de Ribbing y realizar una revisión bibliográfica exhaustiva sobre el tema.

Improvement of Bone Health and Initiation of Puberty Development in Camurati-Engelmann Disease With Glucocorticoid and Losartan Treatment: A Case Report and Review of Literature.

Camurati-Engelmann Disease (CED) is a rare sclerosing bone disease, sometimes associated delayed puberty. The treatment effect of glucocorticoid and angiotensin II receptor blocker (ARB) in bone health and puberty development remain unclear. We report a case of an 18-year-old girl who presented for a history of an enlarged head, pain of lower limbs, and no menstrual onset or breast development. Radiographs revealed thickening of skull and cortices in the diaphysis but sparse bone trabeculae in the spine and metaphysis. Sanger sequencing detected a mutation of c. 652C>T (p. R218C) in the gene TGFB1 and confirmed the diagnosis of CED. After treatment of a medium-to-small dosage of prednisone and losartan for 28 months, we observed improvement of bone mass in spine and hip and body fat mass and found initiation of puberty development. By a systemic review of current treatment strategies in patients with CED, we found that most cases reported relief of bone pain with treatment of glucocorticoid or ARB, but none has reported the outcome of hypogonadotropic hypogonadism. We propose that long-term use of glucocorticoid combined with ARB may inhibit the activation of TGFß1 in CED, improve adipogenesis, and thus initiate puberty development and improve the bone mass in spine and hip.

Looking for the skeleton in the closet-rare genetic diagnoses in patients with diabetes and skeletal manifestations.

AIMS: The precision medicine approach of tailoring treatment to the individual characteristics of each patient has been a great success in monogenic diabetes subtypes, highlighting the importance of accurate clinical and genetic diagnoses of the type of diabetes. We sought to describe three unique cases of childhood-onset diabetes in whom skeletal manifestations led to the revelation of a rare type of diabetes. METHODS : Case-scenarios and review of the literature. RESULTS: Case 1: A homozygous mutation in TRMT10A, a tRNA methyltransferase, was identified in a 15-year-old boy with new-onset diabetes, developmental delay, microcephaly, dysmorphism, short stature and central obesity. The progressive apoptosis of pancreatic beta cells required insulin replacement therapy, with increased demand due to an unfavorable body composition. Case 2: Congenital generalized lipodystrophy type 1 was suspected in an adolescent male with an acromegaloid facial appearance, muscular habitus, and diabetes who presented with a pathological fracture in a cystic bone lesion. A homozygous mutation in AGPAT2, an acyl transferase which mediates the formation of phospholipid precursors, was identified. Leptin replacement therapy initiation resulted in a remarkable improvement in clinical parameters. Case 3: A 12-year-old boy with progressive lower limb weakness and pain was diagnosed with diabetic ketoacidosis. Diffuse diaphyseal osteosclerosis compatible with the diagnosis of Camurati-Engelmann disease and a heterozygous mutation in TGFß1 were identified. Preservation of euglycemia by insulin replacement relieved pain, suggesting that the diabetic milieu may have augmented TGFß1 overexpression. CONCLUSION: Unraveling the precise genetic cause for the clinical manifestations led to the prediction of phenotypic manifestations, and enhanced the clinical outcomes.

Efficacy of denosumab therapy after alendronate treatment for a 66-year-old woman with Camurati-Engelmann disease and osteoporosis: a case report.

Camurati-Engelmann disease (CED) is characterized by hyperostois of multiple long bones. Although several treatments for CED complicated with osteoporosis have been described, it remains controversial whether such therapy is suitable for osteoporotic CED patients. We retrospectively enrolled a 66-year-old female patient with osteoporosis in CED who underwent denosumab therapy for 14 months. Denosumab was commenced after 3 years of alendronate treatment. Fourteen months later, lumbar and total hip bone mineral density showed gains of 5.9% and 6.4%, respectively. Bone turnover markers were also improved during follow-up. No fractures or other complications were recorded during the observational period. This is the first study describing denosumab treatment for an osteoporotic CED patient. Our findings indicate that denosumab is an effective therapy option for osteoporosis in CED.

Bone-targeted delivery of TGF-ß type 1 receptor inhibitor rescues uncoupled bone remodeling in Camurati-Engelmann disease.

Camurati-Engelmann disease (CED) is a genetic bone-modeling disorder mainly caused by mutations in the gene that encodes transforming growth factor-ß1 (TGF-ß1). Symptoms of CED include bone pain, fractures, and dysplasia. Currently, effective therapies for bone fracture and dysplasia in CED are urgently needed. We have demonstrated that TGF-ß1 is a coupling factor for bone remodeling and is aberrantly activated in CED. Daily injection of TGF-ß type 1 receptor inhibitor (TßR1I) attenuated CED symptoms, but this systemic administration caused serious side effects. In this study, we created a conjugate linking TßR1I and alendronate, which delivered TßR1I specifically to bone. After weekly injection of the conjugate for 8 weeks, normal bone morphology and remodeling in CED mice was maintained with a minimum effective dose 700 times lower than TßR1I injection. Additionally, we found that the conjugate restored normal bone turnover by reducing the number of osteoblasts and osteoclasts, maintained a regular osteogenic microenvironment by regulating the formation of CD31 and Endomucin double-positive vessels, and preserved ordinary bone formation via inhibition of the migration of leptin-receptor-positive cells. Thus, targeting delivery of TßR1I to bone is a promising therapy for CED and other uncoupled bone remodeling disorders.

Imaging features and differential diagnosis of multiple diaphyseal sclerosis: A case report and review of literature.

RATIONALE: Multiple diaphyseal sclerosis (MDS), known as Ribbing disease, is a rare congenital bone disease resulting from autosomal recessive inheritance. The case study involved a 22-year-old female patient who had been diagnosed with chronic sclerosing osteomyelitis due to lack of knowledge about MDS. Previous studies reported rarely on this condition. PATIENT CONCERNS: A 22-year-old female with MDS was analyzed. DIAGNOSES: MDS is characterized radiographically by a fusiform widening of the diaphyseal portion of the long bones, which is caused by a thickening of the cortex with obstruction of the medullary cavity. The pathologies are observed utilizing diagnostic imagery and are often difficult to identify. INTERVENTION: The patient was following a suggested regimen of oral celecoxib capsules at 200 mg/day for 6 days. OUTCOMES: The patient's diagnosis was revised to the rare condition of Ribbing disease by reviewing the clinical history and distinctive radiography images and because the symptoms were alleviated by celecoxib capsule. We also present a review of the literature on the diagnosis and differential diagnosis of MDS based on clinical and imaging features. LESSONS: MDS is rare and may often be initially misdiagnosed as another type of sclerosing bone dysplasia, thus, it is important to be aware of the existence of MDS. Once MDS is suspected, differential diagnosis should be performed to exclude other sclerosing bone dysplasias, taking into account clinical history, distinctive radiographic appearance, distribution, and laboratory and histopathologic findings. Laboratory evaluation and pathologic findings are nonspecific but assist in excluding other diagnoses. More evidence is needed to illustrate the effectiveness of medical or surgical treatments for patients with MDS.

Pain improvement in Camurati-Engelmann disease after anti-TNFα therapy.

Camurati-Engelmann disease (CED) is a rare disorder included in the group of craniotubular hyperostosis diseases. Corticosteroids are used for pain management in CED, but in refractory or corticosteroid-non-tolerant patients, pain management is limited. We report the case of a woman with CED diagnosed in early infancy whose initial complaints included persistent bone pain associated with progressive functional disability. She was treated with steroids but over time became dependent on higher doses with only mild pain relief. In her third decade, she was diagnosed with ulcerative colitis (UC) and was treated with mesalazine, azathioprine and prednisolone. Due to recurrent exacerbations of UC, treatment was changed to infliximab, an antitumour necrosis factor-alpha (TNFα). Remission of UC was achieved and CED-associated pain also improved with infliximab. This is the first report showing a possible role of anti-TNFα in pain management in CED with unsatisfactory response to steroids.

Camurati-Engelmann disease-a rare cause of tetany identified on bone scintigraphy: A case report.

RATIONALE: Camurati-Engelmann disease (i.e., progressive diaphyseal dysplasia) is an extremely rare autosomal dominant bone disorder. The most common clinical manifestations were chronic skeletal pain, waddling gait, muscular weakness. PATIENT CONCERNS: We described that a 27-year-old male with a 1-year history of intermittent tetany was referred for bone scintigraphy. The whole body bone scan images showed abnormal increased uptake of the tracer in the long bones of the upper and lower extremities as well as in the skull. DIAGNOSES: Combined the family history, the findings of the images and the genetic study, the diagnosis of Camurati-Engelmann disease was confirmed. INTERVENTIONS AND OUTCOMES: The patient responded well to the treatment of calcium gluconate. LESSONS: Bone scintigraphy would be helpful in the diagnosis and assessing the severity of Camurati-Engelmann disease.