Hereditary multiple osteochondromas (HMO), previously known as hereditary multiple exostoses (HME), is a congenital skeletal developmental anomaly characterized by multiple osteochondromas that commonly grow outward from the metaphyses of long bones. Hereditary multiple exostoses is an autosomal dominant genetic disease characterized by multiple cartilage growth disorders, which affect the long bones of the limbs, scapula, and ribs, among others. Consensus on the diagnosis and treatment of spinal involvement is relatively lacking. For such patients, experience in terms of clinical screening, preoperative evaluation, surgical intervention indications and timing, surgical expertise and lessons learned, and follow-up is needed and critical. This review focuses on the clinical evaluation and orthopedic surgical treatment of HME patients with spinal involvement. It summarizes the patients' diagnosis, clinical features, and treatment strategies based on evidence from the published literature. The clinical manifestations, location of onset, and surgical intervention are summarized in detail in this review. The above contents will help improve the clinical diagnosis and treatment level of HME patients with spinal involvement internationally.
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder characterized by an insidious onset, while its underlying pathogenesis has not yet been fully explored. Identifying and accurately localizing the causative tumors in TIO remains highly challenging in clinical practice. Although complete surgical excision following precise diagnosis is currently considered the most effective treatment approach, surgical management strategies still require optimization, and recurrence may occur even after tumor resection. TIO is primarily recognized as a metabolic bone disease driven by excessive secretion of fibroblast growth factor 23 (FGF23) by tumors; however, its detailed etiological features and molecular pathogenic mechanisms remain unclear. Besides FGF23, other phosphate-regulating hormones and pathogenic genes are also believed to participate in disease development. A clearer understanding of FGF23-mediated phosphate regulation, including hormone secretion, circulation, transport, and interactions with target organs, is critical for early diagnosis and the development of effective therapeutic strategies. Further investigation into the mechanisms responsible for refractory and recurrent TIO is also needed. Integrated multi-omics approaches are expected to provide deeper insight into the complex pathogenic basis of TIO, supporting the development of improved diagnostic and therapeutic strategies. This review summarizes recent progress in understanding the etiology and pathogenesis of TIO, intending to improve disease comprehension and facilitate more effective clinical diagnosis and treatment.
Critical-sized bone defect repair remains a major challenge in orthopaedics and tissue engineering. Polyetheretherketone (PEEK) has attracted wide attention due to its excellent mechanical compatibility and radiological transparency; however, its inherent bioinertness and insufficient antibacterial properties restrict its clinical utility. In recent years, the incorporation of graphene oxide (GO) has markedly improved the biological performance of PEEK. GO can increase surface hydrophilicity and roughness, enhance protein/ion adsorption, and promote osteoblast adhesion and differentiation, while simultaneously strengthening antibacterial and immunomodulatory effects without compromising, and in some cases even enhancing, mechanical performance. In vitro studies demonstrate that GO-PEEK stimulates osteogenic gene expression and mineralized nodule formation, while in vivo animal models confirm superior osseointegration and new bone formation compared with controls. Synergistic modifications, such as combination with hydroxyapatite, metallic ions, or antimicrobial peptides, further amplify both osteogenic and antibacterial outcomes. Nevertheless, clinical translation of GO-PEEK remains hampered by challenges including long-term stability, potential particulate-related risks, the dynamic balance between antibacterial and osteogenic functions, and issues of manufacturing scalability, consistency, and sterilization compatibility. Future research should focus on establishing a “structure–property–safety” design paradigm, developing temporally programmed multifunctional strategies, and advancing 3D-printed personalized fabrication, with low-load applications such as alveolar or cranial bone repair as potential pioneer indications. Overall, GO-PEEK composites exhibit significant promise in contexts such as post-tumour bone reconstruction, dental implantation, and spinal or joint implants, and are expected to achieve successful clinical translation under evidence-based validation and standardised manufacturing pathways.The Translational Potential of this Article: The findings of this review highlight the potential of graphene oxide-modified PEEK (GO-PEEK) composites as next-generation orthopaedic biomaterials. By integrating enhanced osteogenic activity, antibacterial efficacy, and immunomodulatory capacity into a mechanically compatible and radiolucent polymer, GO-PEEK offers a multifunctional platform for bone repair. Importantly, its promising performance in vitro and in vivo provides a foundation for translation into clinical contexts such as dental implants, spinal fusion cages, and tumour-related bone defect reconstruction. Addressing challenges in long-term stability, sterilization compatibility, and large-scale manufacturing will be critical to establish a clear regulatory and translational pathway from laboratory research to clinical practice.
BACKGROUND:Due to its occult position, complex anatomical structure, and spatial relationships, the causative tumor of Tumor-Induced Osteomalacia (TIO) in the hip region is quite difficult to detect and qualitatively diagnose in clinical practice. In this regard, clinicians often lack sufficient knowledge about such tumors, leading to frequent missed diagnoses, misdiagnoses, and unreasonable treatment. OBJECTIVE:This study aimed to investigate the clinical characteristics of TIO patients with culprit soft tissue tumors in the hip region and evaluate the effect of surgical treatment on these individuals to improve clinicians' understanding of the rare phenomenon. METHODS:The clinical data of all patients, from January 2013 to January 2023, who underwent surgical treatment for hip located culprit soft tissue tumors by the subspecialty group on bone and soft tissue tumors at our institution, were retrospectively analysed. Specifically, the clinical characteristics and therapeutic effects were examined and the patients' clinical experience was summarized. RESULTS:Twenty-two patients, who met the inclusion criteria, were included. All patients experienced varying degrees of bone pain, commonly accompanied by weakness (16/22) and limited mobility (21/22), and 10 patients (45.5%) experienced a significant reduction in body height during the course of the disease. All patients underwent orthopedic surgery in the hip region, as hypophosphatemia occurred in all of them. Pathological diagnosis was confirmed to be consistent with causative tumors of TIO. All patients experienced a gradual increase in serum phosphorus postoperatively during short-term follow-up. The follow-up period was between 1 and 10 years, and the postoperative serum phosphorus levels were monitored at our hospital or other facilities close to the patients. CONCLUSIONS:Oncogenic soft tissue tumors for TIO in the hip region are occult, making clinical misdiagnoses or missed diagnoses highly likely. Therefore, enhancing the clinician's understanding of this rare condition is imperative. Notably, for TIO patient whose culprit tumor can be located, complete surgical resection of the causative tumor is the best treatment option. Furthermore, close postoperative monitoring of serum phosphorus is necessary, and patients should be subjected to long-term follow-up for prompt detection of recurrent conditions.
ABSTRACT Objective Tumor‐induced osteomalacia with the culprit tumor located in the knee joint is rare in clinical practice, and previous literature has only been seen in case reports, which pose great challenges to the clinical diagnosis and treatment of such patients. The purpose is to elucidate clinical characteristics and orthopedic surgical treatment experience of tumor‐induced osteomalacia (TIO) with causative tumor located in the knee joint region. Methods Clinical data of all consecutive TIO patients with culprit tumors located in the knee joint region was retrospectively analyzed. All patients were surgically treated by an orthopedic bone and soft tissue tumor sub‐professional team at Peking Union Medical College Hospital from January 2015 to January 2025. The clinical distribution feature and surgical effects were analyzed, and clinical practice experience was presented. Results All nine patients were included in this study. All patients exhibited varying degrees of bone pain and 100% (9/9) of the patients had limited mobility, often accompanied by difficulties in sitting up, walking, and weakness or fatigue. Approximately 44.4% (4/9) of the patients had significantly shorter height after initial symptoms appeared. All patients underwent a total of 10 operations to control the causative tumors in the knee joint region. Culprit tumors were located in the patella (one case), infrapatellar fat pad (three cases), suprapatellar capsule (one case), popliteal fossa (three cases), and the entire knee joint (one case), respectively. There was only one case of skeletal involvement, one case with involvement of bones and soft tissues, and seven cases with soft tissue causative tumors. All the patients had a gradual increase in blood phosphorus levels in the short term after the first orthopedic surgery, after a follow‐up of 12 months to 10 years. During the follow‐up, no patients experienced recurrence. Conclusion The causative tumor for TIO in the knee joint region is hidden and has diverse locations; however, there is no established orthopedic surgical intervention strategy for these rare entities in clinical practice. Due to the unique anatomical location and complex structure of the knee joint, orthopedic surgeons can adopt different surgical approaches to completely remove the causative tumor. For these patients, the prognosis is satisfactory after complete tumor resection, and the condition can be effectively improved. These findings may help to improve the clinical diagnosis and treatment level of orthopedic physicians for this rare entity.
CONTEXT:Denosumab is approved for treating hypercalcemia of malignancy, but data on its efficacy for hypercalcemia related to primary hyperparathyroidism (PHPT) are limited. OBJECTIVE:To compare the efficacy and safety of denosumab with zoledronic acid in PHPT-related hypercalcemia. METHODS:We retrospectively collected data from 29 PHPT patients with moderate/severe hypercalcemia (corrected serum calcium [CSC] ≥ 3.0 mmol/L) treated with denosumab (60 or 120 mg; Dmab group) and CSC-matched 29 PHPT patients treated with zoledronic acid (4 mg; ZA group). The primary efficacy outcome was the change of CSC (ΔCa), while secondary outcomes included the response proportion, time to response, and duration of response. Safety data were also collected. RESULTS:Both groups showed significant reductions in CSC levels (Dmab: 3.37 ± 0.37 mmol/L to 2.64 ± 0.33 mmol/L, P < .01; ZA: 3.41 ± 0.32 mmol/L to 2.57 ± 0.23 mmol/L, P < .01), with similar ΔCa. In the Dmab group, 82.8% (24/29) responded with CSC levels below 3.0 mmol/L, and 72.4% (21/29) achieved complete response (CR, serum CSC less than 2.7 mmol/L), comparable to the ZA group. The time to CR was shorter for ZA (3.0 vs 7.0 days, P < .01), while Dmab had a longer duration of response (19.0 vs 13.0 days, P = .02). Hypocalcemia occurred in 6.9% (2/29, both with chronic kidney disease stage 3b) of Dmab patients, while none in the ZA group. CONCLUSION:A single 60-mg dose of denosumab effectively reduces serum calcium levels in PHPT patients with moderate/severe hypercalcemia, at least maintaining efficacy for a median of nearly 3 weeks without serious adverse events.
BackgroundAugmented reality (AR) technology is gradually being applied in surgical teaching as an innovative teaching method. Developing innovative teaching methods to replicate clinical theory and practical teaching scenarios, simulate preoperative planning and training for bone tumor surgery, and offer enhanced training opportunities for young physicians to acquire and apply clinical knowledge is a crucial concern that impacts the advancement of the discipline and the educational standards for young orthopedic physicians.ObjectiveThis study explores the application effect of augmented reality technology in anatomy teaching and surgical clinical teaching for spinal tumor.MethodsThe method utilizes virtual reality and augmented reality technology to present a spinal tumor model and the surgical process of percutaneous vertebroplasty. We conducted a random selection of 12 students forming into the augmented reality teaching group and 13 students forming into the traditional teaching group among the 8-year medical students from Peking Union Medical College and Tsinghua University, ensuring that the age and learning stage of the students in both groups were similar. Two groups of students were taught using traditional teaching methods and augmented reality technology-assisted teaching methods, respectively. A questionnaire survey was conducted after class to assess the quality of course instruction, student motivation in learning, their proficiency in anatomical structures, their comprehension of spinal tumor growth and metastasis, and their understanding and proficiency in percutaneous vertebroplasty.ResultsThis study was the first to apply augmented reality technology in teaching, using spinal tumors and percutaneous vertebroplasty as examples, a head-mounted augmented reality device was used to create learning scenarios, presenting the complex three-dimensional spatial structure intuitively. The two groups of students differ significantly in their rating of teaching quality, enthusiasm for learning, knowledge of anatomical features, understanding of spinal trabecular structure, and understanding of steps in percutaneous vertebroplasty. The augmented reality technology-assisted teaching system demonstrates outstanding advantages.ConclusionAugmented reality technology has great potential and broad prospects in teaching bone tumors, which can help improve the visualization, interactivity, and three-dimensional spatial sense of medical teaching in spinal tumor. The application and development prospects of using augmented reality technology for anatomy instruction, surgical teaching, and simulation training are extensive.
Objective The orthopedic surgical treatment strategies for patients with tumor‐induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in‐depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor‐induced osteomalacia (TIO), whose causative tumors are located in the hip bones. Methods A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub‐professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery‐related data, perioperative changes in blood phosphorus levels, and postoperative follow‐up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non‐normally distributed data are shown as the means and 25th and 75th interquartile ranges. Results The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. Conclusion In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.
A 41-year-old man sought treatment at the orthopedics clinic.He had experienced back pain for 20 days, with persistent pain radiating to the left buttock.He reported experiencing gout for one year and then underwent surgery for the removal of gouty stones on the right index finger, the dorsum and first metatarsophalangeal joint of the right foot, left knee, and left ankle one year before.After the surgery, the patient received regular oral treatment of 40 mg qd of febuxostat, with satisfactory uric acid control recently.In addition, the patient had suffered from hypertension for approximately one year.Examination by an orthopedic specialist did not identify any specific positive signs, except for the slightly decreased muscle strength of left lower limb (grade V-).Computed tomography of the lumbar spine showed multiple lesions in the left appendage of the L3 vertebra, with osteogenic swelling and involvement of the spinal canal (Figure 1A and1B).Lumbar magnetic resonance imaging also revealed abnormal signals around the left appendage of L3 and in the spinal canal (Figure 1C), involving the spinal canal and left erector spinae muscle.Bone scanning indicated that this represented an abnormality at the left edge of the L3 vertebral body, suggesting a possible benign lesion.In view of the patient's medical history, it was considered that gouty stones in the spinal canal may have caused spinal cord compression.Thus, we performed complete posterior resection of the lesions at the L3 appendage and the partial vertebral lesion (Figure 1D), together with spinal canal decompression, internal fixation of an L2-L4 pedicle screw, and bone graft fusion.
Objective: To evaluate the efficacy and prognosis of percutaneous vertebroplasty/kyphoplasty (PVP/PKP) in patients with newly diagnosed multiple myeloma (NDMM). Methods: Clinical data of NDMM patients who underwent PVP/PKP during front-line regimen at Peking Union Medical College Hospital from January 1, 2003, to June 30, 2023, were analyzed. Patients with comparable bone diseases not receiving orthopedic surgery were selected as controls. Visual analogue scale (VAS) score, progression-free survival (PFS), and overall survival (OS) were compared. Results: Baseline characteristics were matched between the surgical group (n = 51 with 56 surgeries) and nonsurgical group (n = 102), including demographics, tumor load, International Staging System (ISS), bone diseases, cytogenetic abnormalities, first-line treatment, and autologous stem-cell transplantation (ASCT). Bone lesions for PVP/PKP were located at thoracic vertebrae (53.6 %, 30/56) or lumbosacral vertebrae (46.4 %, 26/ 56). The postoperative VAS score was significantly improved (2.25 +/- 0.81 vs 5.92 +/- 1.05, P < 0.001). The median follow-up time was 51[38-70] months. Kaplan-Meier survival analysis suggested that both PFS (37 [17-89] vs 23[12-61] months, HR 0.648, 95 %CI 0.431-0.973, P = 0.047) and OS (not reached vs 66[28-NR] months, HR 0.519, 95 %CI 0.296-0.910, P = 0.045) were significantly prolonged in the surgical group. COX multivariate analysis suggested that PVP/PKP was an independent prognostic factor for PFS (P = 0.021, HR 0.589, 95 %CI 0.376-0.922) and OS (P = 0.038, HR 0.496, 95 %CI 0.255-0.963). Subgroup analysis confirmed that patients with ISS II/III or non-ASCT achieved better PFS and OS in the surgical group (PFS: P = 0.033, P = 0.040; OS: P = 0.024, P = 0.018 respectively), while similar survival outcome was observed in patients with ISS I or ASCT between two groups. Conclusion: For NDMM patients, not only does PVP/PKP alleviate bone pain, meanwhile, it improves the PFS and OS in advanced subpopulation or non-transplant myeloma patients, which suggests that shortening the gap from symptom onset to diagnosis by orthopedic surgery favors clinical prognosis.
Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.Cite this article: Bone Joint Res 2024;13(12):725–740.
Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is very rare, with about 1000 reported cases globally. Removing most TIO culprit tumors requires the evaluation and intervention of orthopedic doctors. However, orthopedic doctors often have a poor understanding of the optical treatment of TIO due to its rarity. In addition, most TIO patients lack specific clinical manifestations. Also, the clinical localization and qualitative diagnosis of TIO are difficult and thus can easily be misdiagnosed and mistreated. Furthermore, the true incidence rate of TIO may be underestimated. Although many breakthroughs have been made in exploring the pathogenesis, clinical diagnosis, and treatment of TIO, rational and standardized orthopedic surgical treatment experience summary and sorting for TIO patients are lacking. In this article, the recent experience and progress in the field of orthopedic surgical treatment for TIO globally have been summarized, providing a theoretical basis and new clinical practice guidance for the rational treatment of TIO patients.
Objective To investigate the clinical symptoms experienced by patients with thoracic spinal tumors and verify the associated symptoms that are predictive of a decline in muscle strength in the lower limbs. Methods A single-center, retrospective cross-sectional study was conducted on in-patients diagnosed with epidural thoracic spinal tumors between January 2011 and May 2021. The study involved a review of electronic medical records and radiographs and the collection of clinical data. The differences in clinical manifestations between patients with constipation and those without constipation were analyzed. Binary logistic regression analyses were performed to identify risk factors associated with a decline in muscle strength in the lower limbs.Results A total of 227 patients were enrolled, including 131 patients with constipation and 96 without constipation. The constipation group had a significantly higher proportion of patients who experienced difficulty walking or paralysis compared to those without constipation prior to surgery (83.2% vs. 17.7%, χ2 = 99.035,P < 0.001). Constipation (OR = 9.522, 95%CI: 4.150-21.849, P < 0.001) and urinary retention (OR = 14.490, 95%CI: 4.543-46.213, P < 0.001) were independent risk factors for muscle strength decline in the lower limbs. Conclusions The study observed that patients with thoracic spinal tumors who experienced constipation symptoms had a higher incidence of lower limb weakness. Moreover, the analysis revealed that constipation and urinary retention were independent risk factors associated with a preoperative decline in muscle strength of lower limbs.