One of the most important tasks in forensic anthropology is the construction of the biological profile, classically defined as a set of four basic biological descriptors: biological sex, age-at-death, ancestry, and stature. Yet, our empirical and technological abilities in reconstructing the life experiences and health from skeletal remains far exceed these four parameters and forensic anthropology could benefit from further descriptors in the search for an identity. In this paper, we propose the inclusion of two other investigations to forensic anthropology practice to implement the already known biological profile: the interpretation of bone disease and lesions, and forensic toxicology on unconventional biological matrices. These analyses can provide information regarding health, habits, and disease burden, and by implementing them in our practice of forensic anthropology, they have the potential to improve the biological profile. We also propose a new term that can include not only the classical biological profile but also further descriptors, namely, the \"biocultural profile\".

UNASSIGNED: Children with sickle cell disease (SCD) are more likely to have deficient serum levels of vitamin D for bone metabolism. However, appropriate interventions are essential to prevent its progression and alleviate symptoms.
UNASSIGNED: The aim of this study is to determine interventions for managing bone disease in children with SCD.
UNASSIGNED: This study uses a scoping review. A literature review was conducted using PubMed, CINAHL, ScienceDirect, Scopus, and Google Scholar search engines. The study was eligible for inclusion if it included articles published from 2013 to 2023, full-text, and original study design. Study quality was assessed using the Joanna Briggs Institute (JBI) appraisal tool.
UNASSIGNED: This review identified six studies and 114 children with SCD, including 57 boys (50%) and 57 girls (50%). The majority of SCD types experienced were HbSS (86.84%), HbS-B0 Thal (7.01%), HbSC (5.27%), and the HbSS Arab-Indian haplotype (0.88%). Bone disease problems that often arise in children with SCD include Avascular Necrosis (AVN) (78.08%), Osteonecrosis of the Femoral Head (ONFH) (18.42%), and other bone problems (3.50%). Meanwhile, four types of intervention findings were used in managing bone disease among children with SCD: 1). Surgical procedures 53 (41.09%) included total hip arthroplasty (THA), Osteotomy, and Multiple epiphyseal drilling with Autologous Bone Marrow Implantation (AMBI); 2). Invasive procedures 67 (51.93%) included intravenous bisphosphonates, hydroxyurea (HU), and core decompression (CD) with bone marrow aspirate concentrate injection: 3). Oral pharmacological or Vitamin D3 (cholecalciferol) 4 (3.10%); 4). Non-pharmacology or physical therapy 5 (3.88%).
UNASSIGNED: Our findings highlight that surgical, invasive, pharmacological, and physical therapy interventions positively impact increasing bone mineral density (BMD) and functional improvement of bone disease among children with SCD. The interventions provided excellent functional outcomes with minimal complications and no life-threatening side effects.

The Neurofibromatosis Type 1 (NF1) RASopathy is associated with persistent fibrotic nonunions (pseudarthrosis) in human and mouse skeletal tissue. Here, we first performed spatial transcriptomics to define the molecular signatures across normal endochondral healing following fracture in mice. Within the control fracture callus, we observed spatially restricted activation of morphogenetic pathways, such as TGF-β, WNT, and BMP. To investigate the molecular mechanisms contributing to Nf1-deficient delayed fracture healing, we performed spatial transcriptomic analysis on a Postn-cre;Nf1flox/- (Nf1Postn) fracture callus. Transcriptional analyses, subsequently confirmed through p-SMAD1/5/8 immunohistochemistry, demonstrated a lack of BMP pathway induction in Nf1Postn mice. To further inform the human disease, we performed spatial transcriptomic analysis of fracture pseudarthrosis tissue from a NF1 patient. Analyses detected increased MAPK signaling at the fibrocartilaginous-osseus junction. Similar to the Nf1Postn fracture, BMP pathway activation was absent within the pseudarthrosis tissue. Our results demonstrate the feasibility to delineate the molecular and tissue-specific heterogeneity inherent in complex regenerative processes, such as fracture healing, and to reconstruct phase transitions representing endochondral bone formation in vivo. Furthermore, our results provide in situ molecular evidence of impaired BMP signaling underlying NF1 pseudarthrosis, potentially informing the clinical relevance of off-label BMP2 as a therapeutic intervention.

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.
目的： 探讨地舒单抗（DENOS）与唑来膦酸（ZOL）治疗新诊断多发性骨髓瘤骨病（MBD）的疗效及安全性。 方法： 回顾性分析2021年3月1日至2023年6月30日解放军总医院第五医学中心血液病医学部收治的80例新诊断MBD患者的临床资料。18例伴重度肾损害（SRI）患者[内生肌酐清除率（CrCl）<30 ml/min]均接受DENOS治疗，62例非SRI患者分为DENOS组（30例）和ZOL组（32例）。 结果： 80例MBD患者中26例（33%）发生低钙血症，22例发生于第1次用药后。非SRI患者中DENOS组低钙血症发生率高于ZOL组[20%（6/30）对13%（4/32），P=0.028]，SRI患者低钙血症发生率为89%（16/18）。多因素分析显示，CrCl<30 ml/min与DENOS治疗后低钙血症相关（P<0.001）。抗骨吸收药物治疗1个月后，DENOS组SRI、非SRI患者血清Ⅰ型胶原交联羧基端肽β特殊序列降低率大于ZOL组（68%对59%对27%，P<0.001），DENOS组SRI、非SRI患者血清Ⅰ型原胶原氨基端前肽升高率大于ZOL组（34%对20%对11%，P<0.05）。抗骨吸收药物治疗后各组全段甲状旁腺激素升高。所有患者均未发生抗骨吸收药物相关颌骨坏死及肾脏不良事件，各组血液学总有效率、完全缓解率、严格意义的完全缓解率差异均无统计学意义（P值均>0.05），中位无进展生存及总生存时间均未达到。 结论： DENOS治疗MBD具有较强的抗骨吸收作用和低肾毒性，低钙血症是常见不良反应，多为轻中度且可控。.

BACKGROUND: Cherubism is known as a very rare autosomal dominant familial disorder of childhood caused by a mutation in the SH3BP2 gene on 4p16.3. It has not yet been observed at birth and is usually diagnosed in children aged 2-7. Here, we present a non-hereditary case of cherubism at a very early age.
METHODS: A 6-month-old girl presented with bilateral progressive jaw enlargement. On physical examination, bilateral asymmetrical jaw enlargement, predominantly on the left side, and some enlarged, non-tender, mobile submandibular lymph nodes were detected. No other abnormality was observed. Further investigations with radiology suggested cherubism and Burkitt\'s lymphoma as differential diagnoses. Later on, histopathologic evaluations were suggestive of cherubism. No surgical interventions were indicated, and the child is on regular follow-ups.
CONCLUSIONS: Non-hereditary Cherubism, despite scarcity, can present in children below two years of age, even as early as the beginning of primary dentition. Accurate and swift diagnosis is essential to avert physical and psychological complications. Our case report shows the importance of keeping cherubism in mind as a differential diagnosis of bone disease, even in children under a year old, and the value of interdisciplinary collaboration in dealing with rare genetic disorders.

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in patients with OI type V. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with an increase in the skeletal progenitor cell population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 had decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupted early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21+ versus p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.

Metastases are complications of primary tumors due to prolonged cancer survival and have become an important issue for oncological patients and the most frequent cause of death and disability. Bone metastases occur at a later stage of cancer disease, and the spine is the most frequent site. To date, the aim of the treatment of metastases remains to be the control of disease and provide a satisfactory quality of life. The decision making of treatment is influenced by several factors such as the status of the primary disease, the number of metastases, site involvement, and the performance status of the patients. For this reason, the treatment of metastases is challenging and undergoes constant development. Therefore, alternative techniques with respect to surgery, which is the first option but not always practicable, and radiochemotherapy are attractive. Lately, electrochemotherapy has emerged as an innovative method for treating various primary and metastatic solid tumors, showing promising outcomes in terms of inducing tumor tissue necrosis and alleviating symptoms. This technique uses electric pulses to increase the uptake of chemotherapy by tumor cells. Despite the initial enthusiasm and good results in the treatment of bone tumors, relatively few papers have described its use in spine metastases. Therefore, we conducted a systemic review of this intriguing topic while also reporting our experience in the use of electrochemotherapy for the treatment of spine metastases.

Fibrous dysplasia (FD) poses a therapeutic challenge due to the dysregulated extracellular matrix (ECM) accumulation within affected bone tissues. In this study, we investigate the therapeutic potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in managing FD by examining its effects on FD-derived cells in vitro. Our findings demonstrate that 1,25(OH)2D3 treatment attenuates the pro-fibrotic phenotype of FD-derived cells by suppressing the expression of key pro-fibrotic markers and inhibiting cell proliferation and migration. Moreover, 1,25(OH)2D3 enhances mineralization by attenuating pre-osteoblastic cellular hyperactivity and promoting maturation towards an osteocytic phenotype. These results offer valuable insights into potential treatments for FD, highlighting the role of 1,25(OH)2D3 in modulating the pathological properties of FD-derived cells.

BACKGROUND: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function.
RESULTS: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation.
CONCLUSIONS: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.