Bi-allelic variants in IPO8 cause a connective tissue disorder associated with cardiovascular defects, skeletal abnormalities, and immune dysregulation.

Dysregulated transforming growth factor TGF-ß signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-ß-dependent SMADs trafficking to the nucleus in vitro. The important in vivo role of IPO8 in pSMAD nuclear translocation was demonstrated by CRISPR/Cas9-mediated inactivation in zebrafish. Consistent with IPO8's role in BMP/TGF-ß signaling, ipo8-/- zebrafish presented mild to severe dorso-ventral patterning defects during early embryonic development. Moreover, ipo8-/- zebrafish displayed severe cardiovascular and skeletal defects that mirrored the human phenotype. Our work thus provides evidence that IPO8 plays a critical and non-redundant role in TGF-ß signaling during development and reinforces the existing link between TGF-ß signaling and connective tissue defects.

Age-related bone diseases: Role of inflammaging.

Bone aging is characterized by an imbalance in the physiological and pathological processes of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis, resulting in exacerbated bone loss and the development of age-related bone diseases, including osteoporosis, osteoarthritis, rheumatoid arthritis, and periodontitis. Inflammaging, a novel concept in the field of aging research, pertains to the persistent and gradual escalation of pro-inflammatory reactions during the aging process. This phenomenon is distinguished by its low intensity, systemic nature, absence of symptoms, and potential for management. The mechanisms by which inflammaging contribute to age-related chronic diseases, particularly in the context of age-related bone diseases, remain unclear. The precise manner in which systemic inflammation induces bone aging and consequently contributes to the development of age-related bone diseases has yet to be fully elucidated. This article primarily examines the mechanisms underlying inflammaging and its association with age-related bone diseases, to elucidate the potential mechanisms of inflammaging in age-related bone diseases and offer insights for developing preventive and therapeutic strategies for such conditions.

Suspected silent pituitary somatotroph neuroendocrine tumor associated with acromegaly-like bone disorders: a case report.

BACKGROUND: Growth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels. CASE PRESENTATION: We report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved. CONCLUSIONS: GH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.

The many faces of sickle cell disease in children: complications in the appendicular skeleton.

Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Musculoskeletal complications of SCD are often the main causes for acute and chronic morbidities in children with manifestations including osteomyelitis, osteoporosis and osteonecrosis. This article aims to familiarise the paediatric radiologist with appendicular skeletal complications of SCD in the paediatric population and their imaging appearance.

RANK-RANKL-OPG Axis in MASLD: Current Evidence Linking Bone and Liver Diseases and Future Perspectives.

Metabolic dysfunction-associated steatotic liver disease (MASLD)-and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage-corresponds to the liver's involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication.

Machine Learning-Driven Biomarker Discovery for Skeletal Complications in Type 1 Gaucher Disease Patients.

Type 1 Gaucher disease (GD1) is a rare, autosomal recessive disorder caused by glucocerebrosidase deficiency. Skeletal manifestations represent one of the most debilitating and potentially irreversible complications of GD1. Although imaging studies are the gold standard, early diagnostic/prognostic tools, such as molecular biomarkers, are needed for the rapid management of skeletal complications. This study aimed to identify potential protein biomarkers capable of predicting the early diagnosis of bone skeletal complications in GD1 patients using artificial intelligence. An in silico study was performed using the novel Therapeutic Performance Mapping System methodology to construct mathematical models of GD1-associated complications at the protein level. Pathophysiological characterization was performed before modeling, and a data science strategy was applied to the predicted protein activity for each protein in the models to identify classifiers. Statistical criteria were used to prioritize the most promising candidates, and 18 candidates were identified. Among them, PDGFB, IL1R2, PTH and CCL3 (MIP-1α) were highlighted due to their ease of measurement in blood. This study proposes a validated novel tool to discover new protein biomarkers to support clinician decision-making in an area where medical needs have not yet been met. However, confirming the results using in vitro and/or in vivo studies is necessary.

Multiple myeloma-A painful disease of the bone marrow.

Multiple myeloma is a bone marrow neoplasia with an incidence of 6/100,000/year in Europe. While the disease remains incurable, the development of novel treatments such as autologous stem cell transplantation, proteasome inhibitors and monoclonal antibodies has led to an increasing subset of patients living with long-term myeloma. However, more than two thirds of patients suffer from bone pain, often described as severe, and knowledge on the pain mechanisms and its effect on their health-related quality of life (HRQoL) is limited. In this review, we discuss the mechanisms of myeloma bone disease, the currently available anti-myeloma treatments and the lessons learnt from clinical studies regarding HRQoL in myeloma patients. Moreover, we discuss the mechanisms of cancer-induced bone pain and the knowledge that animal models of myeloma-induced bone pain can provide to identify novel analgesic targets. To date, information regarding bone pain and HRQoL in myeloma patients is still scarce and an effort should be made to use standardised questionnaires to assess patient-reported outcomes that allow inter-study comparisons of the available clinical data.

Long-term bone outcomes in Italian patients with Gaucher disease type 1 or type 3 treated with imiglucerase: A sub-study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

BACKGROUND: Gaucher disease (GD) is a lysosomal storage disorder. We evaluated the "real-world" effectiveness of first-line imiglucerase on long-term bone outcomes in Italian patients in the International Collaborative Gaucher Group (ICGG) Gaucher Registry. METHODS: Patients treated with imiglucerase for ≥2 years and with bone assessments at baseline and during follow-up were selected. Data on bone pain, bone crises, marrow infiltration, avascular necrosis, infarction, lytic lesions, Erlenmeyer flask deformity, bone fractures, mineral density, and imiglucerase dosage were evaluated. RESULTS: Data on bone manifestations were available for 73 of 229 patients (31.9 %). Bone crises frequency decreased significantly from baseline to the most recent follow-up (p < 0.001), with some improvement observed in bone pain prevalence. Bone pain and bone crises prevalence decreased significantly from baseline at 2 to <4 and 4 to <6 years (all p < 0.05). A low median (25th, 75th percentile) baseline imiglucerase dosage was identified in patients reporting bone pain or bone crises (15.0 [13.7, 30.0] and 22.8 [17.5, 36.0] U/kg once every 2 weeks, respectively). CONCLUSION: Our study suggests that the management of GD in Italy, with regards to imiglucerase dosage, is suboptimal and confirms the need for clinicians to monitor and correctly treat bone disease according to best practice guidelines.

Pediatric focal calvarial lesions: an illustrated review.

Focal skull lesions in children can be diagnostically challenging with a wide variety of potential etiologies. Understanding the diverse pathologies and recognizing their associated clinical and imaging characteristics is crucial for accurate diagnosis and appropriate treatment planning. We review pertinent anatomy of the scalp and calvarium and review different pathologies that can present with focal skull lesions in pediatric patients. These include neoplastic, non-neoplastic tumor-like, congenital, post traumatic, and vascular-associated etiologies. We review the key clinical and imaging features associated with these pathologies and present teaching points to help make the correct diagnosis. It is important for radiologists to be aware of the common and rare etiologies of skull lesions as well as the clinical and imaging characteristics which can be used to develop an accurate differential to ensure a timely diagnosis and initiate appropriate management.

Patellar development after patella instability and early reduction in growing rabbits.

BACKGROUND: Patella-shaped disorder has been considered as a predisposing factor for patella instability. But the influence of early patella reduction for patellar development remains unclear. This study aimed to evaluate whether early operation in patella instability could improve patella morphology in growing rabbits. METHODS: Fifty rabbits (1-month-old) were included in the study. The control group underwent no surgical procedures. The two experimental groups (reduction group and non-reduced group), underwent medial soft tissue restraint release surgery. The reduction group, rabbits underwent the medial soft tissue sutura surgery in order to stabilize the patella 2 months after release surgery. The non-reduced group, rabbits did not undergo suture surgery. Computed Tomography (CT) scans analysis in two experimental endpoints (2, 5 months after release surgery) were selected to evaluate the transverse diameter, thickness, Wiberg index and Wiberg angle. Gross observation was conducted to assess morphological changes of the patella. RESULTS: CT scans showed significant difference in the mean transverse diameter, Wiberg angle between the two experimental groups and the control group 2 months after release surgery. 5 months after release surgery, the indices of patella were found no statistically difference in the reduction group versus the control group. However, the transverse diameter, Wiberg angle in the non-reduced group were significantly differences than that in the reduction group (P < 0.05). Gross observation showed a flattened articular surface of the patella in the non-reduced group. CONCLUSIONS: The results indicated that patella instability may lead to patella-shaped disorder, showing a flattened morphology. Early patella reduction can improve the patella morphology in growing rabbits.

mTOR Signaling Pathway in Bone Diseases Associated with Hyperglycemia.

The interplay between bone and glucose metabolism has highlighted hyperglycemia as a potential risk factor for bone diseases. With the increasing prevalence of diabetes mellitus worldwide and its subsequent socioeconomic burden, there is a pressing need to develop a better understanding of the molecular mechanisms involved in hyperglycemia-mediated bone metabolism. The mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that senses extracellular and intracellular signals to regulate numerous biological processes, including cell growth, proliferation, and differentiation. As mounting evidence suggests the involvement of mTOR in diabetic bone disease, we provide a comprehensive review of its effects on bone diseases associated with hyperglycemia. This review summarizes key findings from basic and clinical studies regarding mTOR's roles in regulating bone formation, bone resorption, inflammatory responses, and bone vascularity in hyperglycemia. It also provides valuable insights into future research directions aimed at developing mTOR-targeted therapies for combating diabetic bone diseases.

Occlusive wound closure prevents prolonged wound discharge-A randomised controlled trial in patients undergoing tumour resection and endoprosthetic reconstruction of the proximal femur because of metastatic bone disease.

Prolonged wound discharge is a common postoperative complication of orthopaedic procedures and a risk factor for implant-related infection. Occlusive wound closure methods have previously been suggested to reduce or even prevent this complication. We performed a randomised controlled trial on 70 patients who underwent surgical treatment for metastatic bone disease involving the proximal femur at our centre between January 2017 and August 2018. At conclusion of the tumour resection and endoprosthetic reconstruction procedure, patients were randomised to either occlusive wound closure (n = 35), using the Dermabond Prineo-22 skin closure system, or routine wound closure with conventional skin staples (n = 35). Skin closure with occlusive wound closure resulted in a lesser degree (P < .0001) and shorter duration of postoperative wound discharge (HR 2.89 [95% CI 1.6-5.05], P < .0018). Compared with staples, surgical wounds were already dry after a mean of 3.5 days [95% CI 3.2-3.9] versus 6.1 days [95% CI 4.8-7.3] (P < .0001). Prolonged wound discharge for 7 days or more was observed in 23% of patients (n = 8) in the Staples-group but was entirely absent in the occlusive wound closure group (P < .003). This study provides strong evidence that occlusive wound closure reduces frequency, degree, and duration of wound discharge in a patient population at particularly high risk for this complication.

Advances in the pathogenesis of multiple myeloma bone disease. / å¤šå‘æ€§éª¨é«“ç˜¤éª¨ç— å‘ç— æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

Multiple myeloma (MM) is a clonal proliferative malignant tumor of plasma cells in bone marrow. With the aging of population in China, the incidence of MM is on the rise. Multiple myeloma bone disease (MBD) is one of the common clinical manifestations of MM, and 80%-90% of MM patients are accompanied by osteolytic lesions at the time of their first visit to the clinic. MBD not only increases the disability rate of patients, but also severely reduces the physical function of patients due to skeletal lesions and bone-related events. Currently available drugs for treating of MBD are ineffective and associated with side effects. Therefore, it is important to find new therapeutic approaches for the treatment of MBD. It is generally believed that the increased osteoclast activity and suppressed osteoblast function are the main pathologic mechanisms for MBD. However, more and more studies have suggested that soluble molecules in the bone marrow microenvironment, including cytokines, extracellular bodies, and metabolites, play an important role in the development of MBD. Therefore, exploring the occurrence and potential molecular mechanisms for MBD from multiple perspectives, and identifying the predictive biomarkers and potential therapeutic targets are of significance for the clinical treatment of MBD.

[Constitutional diseases of bone: clinical flags]. / Quand penser à une maladie osseuse constitutionnelle ?

Constitutional diseases of bone form a heterogeneous group of rare diseases of varied phenotypic presentations with a vast genetic heterogeneity. Detected mostly in childhood, they may also be diagnosed in adulthood. Medical history, clinical examination as well as biological and radiological investigations may lead to the diagnosis, which should be confirmed genetically. Joint limitations, early osteoarthritis, hip dysplasia, bone deformity, enthesopathies, bone fragility or a small height can be warning signs of a constitutional disease of bone. Establishing the diagnosis is crucial to enable optimal medical management with a specialized multidisciplinary team.

Les maladies osseuses constitutionnelles constituent un groupe hétérogène de maladies rares de présentations phénotypiques variées et d'une grande hétérogénéité génétique. Le plus souvent détectées dans l'enfance, elles peuvent également être diagnostiquées à l'âge adulte. L'anamnèse, l'examen clinique et les bilans biologiques et radiologiques permettent d'orienter le diagnostic, qui devra être confirmé par une analyse génétique. Les limitations articulaires, l'arthrose précoce, les dysplasies de hanches, les déformations osseuses, les enthésopathies ou la fragilité osseuse ainsi qu'une petite taille sont des signes d'alerte pour rechercher une maladie osseuse constitutionnelle. Établir le diagnostic est crucial pour permettre une prise en charge optimale, multidisciplinaire et spécialisée.

Bone lesions of Langerhans cell histiocytosis triggered by trauma in children.

BACKGROUND: Bone lesions of Langerhans cell histiocytosis (LCH) may be triggered by trauma. METHODS: The characteristics of pediatric patients in the JLSG-02 study cohort who developed a bone lesion at the trauma site at diagnosis of LCH were analyzed retrospectively. RESULTS: Of the 261 pediatric patients with LCH, 12 (4.6%), of median age 4.9 years, had trauma-triggered bone LCH lesions at diagnosis, making them significantly older than the remaining patients (P = 0.006). Trauma sites included the craniofacial regions in 10 patients and the lumbar spine and pelvis in one patient each. At the time of trauma, six patients had a bump at the site, whereas none had extradural hematomas or bone fractures. The median time from trauma to onset was 4 weeks. Of these 12 patients, three had isolated bone (IB) disease; four had multifocal bone (MFB) disease, including the bone lesion at the trauma site; and five had multisystem disease, including four with lesions in neighboring tissue and one with polyuria (posterior pituitary lesion) more than 1 year before the trauma-triggered bone lesion. Treatment responses were good in all 12 patients and none died, but relapses were observed in two patients, one each with IB and MFB disease. CONCLUSIONS: About 5% of pediatric patients with LCH developed new trauma-triggered bone lesions at a relatively old age. These lesions can manifest as IB, or, in patients with underlying LCH diseases, as MFB or multisystem. Good clinical outcomes were observed in these patients.

Pathogenesis and Treatment of Myeloma-Related Bone Disease.

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/ß-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD.

[Receptor Activator of Nuclear Factor κB Ligand-Receptor Activator of Nuclear Factor κB Signaling Pathway in Myeloma Bone Disease].

Multiple myeloma is an incurable malignant disease characterized by proliferation of clonal plasma cells in the bone marrow.About 90% of the patients with multiple myeloma develop myeloma bone disease(MBD),which seriously affects the quality of life and prognosis of the patients.Traditional therapies for MBD include bisphosphonates,radiotherapy,and surgery.The recent studies have confirmed that the receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB(RANK) signaling pathway plays a key role in MBD,providing a new therapeutic target for MBD.This review summarized the role of RANKL-RANK signaling pathway in the pathogenesis of MBD and the advance in the targeted therapy.

Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group.

In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating physician can consider decreasing the frequency of or discontinuing zoledronic acid treatment. Denosumab can also be considered for the treatment of multiple myeloma-related bone disease, particularly in patients with renal impairment. Denosumab might prolong progression-free survival in patients with newly diagnosed multiple myeloma who have multiple myeloma-related bone disease and who are eligible for autologous stem-cell transplantation. Denosumab discontinuation is challenging due to the rebound effect. The Bone Working Group of the International Myeloma Working Group also found cement augmentation to be effective for painful vertebral compression fractures. Radiotherapy is recommended for uncontrolled pain, impeding or symptomatic spinal cord compression, or pathological fractures. Surgery should be used for the prevention and restoration of long-bone pathological fractures, vertebral column instability, and spinal cord compression with bone fragments within the spinal route.

A possible way to prevent the progression of bone lesions in multiple myeloma via Src-homology-region-2-domain-containing-phosphatase-1 activation.

On the basis of our recent findings, in which multiple receptor-mediated mast cell functions are regulated via a common signaling cascade, we posit that the formation and functioning of osteoclasts are also controlled by a similar common mechanism. These cells are derived from the same granulocyte/monocyte progenitors and share multiple receptors except those that are cell-specific. In both types of cells, all known receptors reside in lipid rafts, form multiprotein complexes with recruited signaling molecules, and are internalized upon receptor engagement. Signal transduction proceeds in a chain of protein phosphorylations, where adaptor protein LAT (linker-for-activation-of-T-cells) plays a central role. The key kinase that associates LAT phosphorylation and lipid raft internalization is Syk (spleen-tyrosine-kinase) and/or an Src-family-kinase, most probably Lck (lymphocyte-specific-protein-tyrosine-kinase). Dephosphorylation of phosphorylated Syk and Lck by activated SHP-1 (Src-homology-region-2-domain-containing-phosphatase-1) terminates the signal transduction and endocytosis of receptors, resulting in inhibition of osteoclast differentiation and other functions. In malignant plasma cells (MM cells) too, SHP-1 plays a similar indispensable role in controlling signal transduction required for survival and proliferation, though BLNK (B-cell-linker-protein), a functional equivalent of LAT and SLP-76 (SH2-domain-containing-leukocyte-protein-of-76-kDa) in B cells, is used instead of LAT. In both osteoclasts and MM cells, therefore, activated SHP-1 acts negatively in receptor-mediated cellular functions. In osteoblasts, however, activated SHP-1 promotes differentiation, osteocalcin generation, and mineralization by preventing both downregulation of transcription factors, such as Ostrix and Runx2, and degradation of ß-catenin required for activation of the transcription factors. SHP-1 is activated by tyrosine phosphorylation and micromolar doses (M-dose) of CCRI-ligand-induced SHP-1 activation. Small molecular compounds, such as A770041, Sorafenib, Nitedanib, and Dovitinib, relieve the autoinhibitory conformation. Activation of SHP-1 by M-dose CCRI ligands or the compounds described may prevent the progression of bone lesions in MM.

Orthopedic Surgical Treatment and Perioperative Complications in Multiple Myeloma Bone Disease: Analysis of a Series (2009-2018).

BACKGROUND: More than 90% of patients with multiple myeloma (MM) develop lytic bone lesions that can be surgically treated for symptomatic relief and functional improvement. METHODS: This was a retrospective observational analytic study conducted between 2009 and 2018, including 58 patients with MM bone disease who underwent 77 orthopedic surgical procedures and were co-managed by internal medicine. Analysis of data related to MM bone disease, different modalities of surgical treatment, perioperative complications, and survival was performed. RESULTS: Median age was 72 years (66.5-77 years) and 56.9% of patients were males; 54.43% of injuries were located in the spine, 27.85% in the pelvis or lower limbs, 15.19% in the upper limbs, and 75.32% of patients had pathologic fractures. In 29.31% of the cases, the bone lesion was the debut of MM. Surgical procedures performed were mainly kyphoplasty (48.05%) and intramedullary nailing (29.87%). The overall complication rate following surgery was 74.03%. Only 20.78% of cases had a surgical complication. Among medical complications, we registered 28.57% transfusion requirements, 25.97% acute renal failures, 24.68% developed an infection, and 10.39% developed hypercalcemia. Patients were followed-up for a mean of 6.13 years and 37.93% suffered a new fracture. The median overall survival time for patients after surgery was 32.9 months (11.6-49). The estimated overall survival at 1, 3, and 5 years after surgery was 81.17%, 57%, and 34.11%, respectively. CONCLUSIONS: The orthopedic surgical treatment of MM bone disease aims to improve symptomatology and patient quality of life; however, these patients have a high risk of perioperative complications and considerable early mortality, making multidisciplinary management with medical specialties essential.