リンパ管腫症／ゴーハム病

Gorham-Stout disease (GSD) is a rare idiopathic osteolytic disorder, and its diagnosis depends on a comprehensive evaluation of clinical, imaging, and pathological findings, alongside the systematic exclusion of other diseases. We report a case of GSD characterized by progressive clavicular bone destruction and resorption following low-energy trauma. Monitoring biochemical markers related to bone turnover is essential for early diagnosis and disease assessment, which is critical for controlling disease progression. The early administration of osteoclast activity inhibitors, combined with active vitamin D supplementation, can improve prognosis. Treatment plans should be individualized based on the lesion site, the patient's age, and specific needs. In clinical practice, the routine internal fixation of fractures without a definitive diagnosis may lead to severe consequences.

Gorham-Stout disease (GSD) is a rare condition characterized by progressive osteolysis and abnormal proliferation of lymphatic vessels. Its pathogenesis involves PI3K/AKT/mTOR pathway hyperactivation, providing a molecular basis for the application of targeted mTOR inhibitors such as sirolimus. This study aims to systematically review the efficacy and safety of sirolimus in treating adult patients with GSD presenting with skeletal manifestations. A systematic review was conducted in accordance with PRISMA 2020 guidelines using PubMed, Scopus, and EMBASE databases. Data from eligible case reports involving adult patients were extracted and analyzed through a qualitative narrative synthesis. Nine case reports involving 9 patients (mean age 39.3 years) met the inclusion criteria. Patients presented with extensive polyostotic involvement and severe complications such as massive pleural effusions or recurrent chylothorax. Sirolimus therapy yielded a therapeutic response in seven out of nine patients, including two complete and five partial responses. Data from these nine case reports suggest that the intervention may effectively halt active osteolysis and promote the resolution of effusions. While the therapy successfully arrested disease progression and induced significant localized bone formation, complete anatomical reossification of all osteolytic lesions was not achieved in the adult cohort. The treatment was generally well-tolerated, with manageable adverse events (acne, mild mouth sores, hyperlipidemia, nausea, and respiratory infection). Targeted sirolimus therapy serves as a potential therapeutic option for adult GSD. It necessitates a long-term, multimodal approach, including concurrent anti-resorptive and continuous imaging follow-up. Current evidence is limited by the reliance on heterogeneous case reports. Multicenter prospective registries or international collaborative cohorts are required to validate our results and establish standardized dosing guidelines.

INTRODUCTION: Primary hyperparathyroidism, though commonly diagnosed through hypercalcemic symptoms, can rarely present as advanced skeletal pathology due to delayed recognition. Metabolic bone disease, including osteitis fibrosa cystica and fragility fractures, represents a late and uncommon manifestation in the modern diagnostic era. CASE REPORT: We report a rare case of a 26-year-old male who presented with bilateral femoral neck fractures following 4.5 years of progressive hip pain. He had a history of parathyroid adenoma excision 2 years prior and was diagnosed with "hungry bone syndrome" postoperatively. Imaging revealed classic skeletal changes of severe metabolic bone disease, including osteolysis, spinal deformities, and multiple cystic lesions. He underwent staged bilateral total hip arthroplasty with good functional recovery over 1 year. CONCLUSION: This case underscores the importance of considering primary hyperparathyroidism in young patients presenting with unexplained skeletal complaints. Early recognition and management are essential to prevent irreversible bone damage and avoid debilitating complications such as bilateral femoral neck fractures.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia caused by cathepsin K deficiency and characterized by osteosclerosis and bone fragility. Recurrent low-trauma fractures and delayed healing represent major orthopedic challenges, particularly when medullary canal narrowing limits surgical options. We report the case of two brothers born to consanguineous parents who presented with short stature, characteristic craniofacial dysmorphism, acro-osteolysis, and recurrent fractures after minor trauma. The older sibling had the more severe skeletal phenotype, with 14 fractures involving both tibiae, the right femur, and right metatarsals. Most fractures were initially managed conservatively, but later injuries required plate-and-screw fixation because intramedullary nailing was not feasible due to marked bone sclerosis and near obliteration of the medullary canal. The younger sibling showed a milder course, with four tibial fractures treated orthopedically. Radiographs in both patients demonstrated diffuse osteosclerosis, persistent patency of cranial sutures, Wormian bones, mandibular hypoplasia, and distal acro-osteolysis, while calcium-phosphate parameters remained within normal limits. The diagnosis of pycnodysostosis was established on clinicoradiologic grounds. These sibling cases highlight the marked intrafamilial variability of pycnodysostosis and the technical difficulties of fracture management in sclerotic bone. Early recognition of the characteristic phenotype is essential to avoid misdiagnosis and to guide long-term multidisciplinary follow-up with individualized orthopedic planning.

Bedinvetmab (Librela/Beransa) is a canine anti-nerve growth factor monoclonal antibody (aNGFmAb) approved for the management of osteoarthritis pain. By neutralizing NGF, it reduces nociceptive signaling and improves comfort. However, NGF plays critical roles in neural, bone, and cartilage homeostasis across species. Multiple studies indicate that NGF contributes to bone remodeling and cartilage repair by modulating osteoblast, osteoclast, and chondrocyte activity, processes that are highly active in osteoarthritic joints. In humans, rodents, and rabbits, inhibition of NGF is associated with rapidly progressive osteoarthritis, a serious adverse event characterized by accelerated joint destruction and collapse, which ultimately prevented regulatory approval of human aNGFmAbs-yet the canine aNGFmAb, bedinvetmab, received marketing authorization. Emerging clinical signals in canine patients raise concern that NGF blockade may similarly mask early structural deterioration, potentially accelerating osteolysis and chondrolysis in both index joints and nonindex joints. Although purportedly rare, those adverse drug events are irreversible and often catastrophic, resulting in rapid joint degeneration, progressive osseous collapse, and fractures, which can occur within months. This stands in contrast to high reported clinician satisfaction rates and underscores the need for careful postmarketing vigilance. Given NGF's integral role in joint biology, objective monitoring strategies are warranted. These strategies should include thorough baseline and follow-up examinations, standardized imaging protocols, diligent adverse event reporting, and, where appropriate, histopathological assessment. Transparent communication of potential risks, along with documented informed consent, is essential to support balanced, clinical decision-making by veterinarians and pet owners.