Subperiosteal Bone Formation Research Articles

A macroscopic assessment of porosity and new bone formation on the inferior pars basilaris: Normal growth or an indicator of scurvy?

ObjectivesThis research aims to determine the aetiology of porosity and subperiosteal new bone formation on the inferior surface of the pars basilaris. MaterialsA total of 199 non-adult individuals aged 36 weeks gestation to 3.5 years, from a total of 12 archaeological sites throughout the UK, including Iron Age (n=43), Roman (n=12), and post-medieval (n=145) sites, with a preserved pars basilaris. MethodsThe pars basilaris was divided into six segments, with porosity (micro and macro) and subperiosteal new bone formation recorded on the inferior surface in scorbutic and non-scorbutic individuals. Scurvy was diagnosed using criteria from the palaeopathological literature that was developed using a biological approach. ResultsThere was no statistically significant difference in microporosity between scorbutic and non-scorbutic individuals in four out of the six segments analysed. There was a significant negative correlation between age and microporosity in non-scorbutic and scorbutic individuals. A significant difference in subperiosteal new bone formation was observed between scorbutic and non-scorbutic individuals. ConclusionsMicroporosity on the inferior pars basilaris should not be considered among the suite of lesions included in the macroscopic assessment of scurvy in non-adult skeletal remains (less than 3.5 years). SignificanceThis study highlights the risk of over diagnosing scurvy in past populations. LimitationsIt is difficult to distinguish between physiological (normal) and pathological (abnormal) bone changes in the skeleton of individuals less than one year of age. Suggestions for further researchFuture research should focus on the analysis of individuals over 3.5 years of age.

MTSS2-related neurodevelopmental disorder: Further delineation of the phenotype

MTSS2-related neurodevelopmental disorder (MTSS2-related NDD) (MIM 620086) is characterized by intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF). The only existing report to date described five individuals who exhibited an identical de novo c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. Herein, we report a new case of MTSS2-related NND in a male dizygotic twin who presented with IDDOF and severe intellectual disability. This patient also displayed additional clinical features, including low functioning autism, hypothyroidism, duodenal obstruction secondary to Ladd's bands, inguinal hernias, cryptorchidism, transient subperiosteal new bone formation, and short stature with delayed bone age, which had not been previously reported in association with the MTSS2-related NDD. Exome sequencing identified the recurrent c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. The mother and the other twin tested negative for the pathogenic variant, while the father's participation in the study was unavailable. This case confirms that the MTSS2-related NDD is caused by the recurrent MTSS2 missense variant p.Arg671Trp. The novel findings identified in our patient expand the phenotypic spectrum associated with this new autosomal dominant entity, but further studies on its genetic and clinical manifestations are still needed.

OSTEOMYELITIS WITH PROLIFERATIVE PERIOSTITIS ASSOCIATED WITH A SECOND PRIMARY MOLAR: CASE REPORT

Osteomyelitis with proliferative periostitis, also called Garre's osteomyelitis, is a rare chronic process characterized by periosteal proliferation reactive to the presence of inflammation. A 4-year-old male patient presented with facial asymmetry on the right side with 3 months of evolution and diffuse pain. Clinical examination revealed an indurated and hyperemic facial tumor and severe trismus, in addition to a decayed second primary molar. Imaging exams revealed periosteal thickening and subperiosteal new bone formation with radiopaque lamination associated with tooth 85. Treatment involved antibiotic therapy, drainage of purulent secretions, and removal of the decayed tooth. After incisional biopsy, microscopic examination showed interconnected bone trabeculae, arranged in parallel and surrounded by osteoblasts. Multinucleated giant cells similar to osteoclasts, fibrous connective tissue with focal of lymphoplasmacytic inflammatory infiltrate, and scattered polymorphonuclear cells confirmed the diagnosis of osteomyelitis with proliferative periostitis. After 7 days there was a decrease of the edema and recovered mouth opening.

Caffey disease is associated with distinct arginine to cysteine substitutions in the proα1(I) chain of type I procollagen

Infantile Caffey disease is a rare disorder characterized by acute inflammation with subperiosteal new bone formation, associated with fever, pain, and swelling of the overlying soft tissue. Symptoms arise within the first weeks after birth and spontaneously resolve before the age of two years. Many, but not all, affected individuals carry the heterozygous pathogenic COL1A1 variant (c.3040C>T, p.(Arg1014Cys)). We sequenced COL1A1 in 28 families with a suspicion of Caffey disease and performed ultrastructural, immunocytochemical, and biochemical collagen studies on patient skin biopsies. We identified the p.(Arg1014Cys) variant in 23 families and discovered a novel heterozygous pathogenic COL1A1 variant (c.2752C>T, p.(Arg918Cys)) in five. Both arginine to cysteine substitutions are located in the triple helical domain of the proα1(I) procollagen chain. Dermal fibroblasts (one patient with p.(Arg1014Cys) and one with p.(Arg918Cys)) produced molecules with disulfide-linked proα1(I) chains, which were secreted only with p.(Arg1014Cys). No intracellular accumulation of type I procollagen was detected. The dermis revealed mild ultrastructural abnormalities in collagen fibril diameter and packing. The discovery of this novel pathogenic variant expands the limited spectrum of arginine to cysteine substitutions in type I procollagen. Furthermore, it confirms allelic heterogeneity in Caffey disease and impacts its molecular confirmation.

Caffey Disease: A Diagnostic Dilemma

Caffey disease is a rare, self limiting condition which usually presents in early infancy. The clinical features include fever, irritability, inflammatory swelling of soft tissue due to acute inflammation of the periosteum and subperiosteal new bone formation. Possible differential diagnoses are osteomyelitis, hypervitaminosis A, scurvy, bone tumours, prolonged use of Prostaglandin E1 (PGE1) and child abuse. Although self-limiting, it can cause diagnostic dilemma leading to delayed diagnosis and unnecessary investigations. Here, we report a case of two month old male infant presenting with painful left scapular mass.

Improved in vivo osseointegration and degradation behavior of PEO surface-modified WE43 magnesium plates and screws after 6 and 12 months

Magnesium is a highly promising candidate with respect to its future use as a material for resorbable implants. When magnesium degrades, hydrogen gas is released. High doses of gas emergence are reported to impair osseointegration and may therefore lead to fixation failure. The successful delay and reduction of the degradation rate by applying plasma electrolytic oxidation (PEO) as a post processing surface modification method for magnesium alloy has recently been demonstrated. The aim of this study was thus to compare the degradation behavior of a WE43-based plate system with and without respective PEO surface modification and to further investigate osseointegration, as well as the resulting effects on the surrounding bony tissue of both variants in a miniature pig model.WE43 magnesium screws and plates without (WE43) and with PEO surface modification (WE43-PEO) were implanted in long bones of Göttingen Miniature Pigs. At six and twelve months after surgery, micro-CT and histomorphometric analysis was performed.Residual screw volume (SV/TV; WE43: 28.8 ± 21.1%; WE43-PEO: 62.9 ± 31.0%; p = 0.027) and bone implant contact area (BIC; WE43: 18.1 ± 21.7%; WE43-PEO: 51.6 ± 27.7%; p = 0.015) were increased after six months among the PEO-modified implants. Also, surrounding bone density within the cortical bone was not affected by surface modification (BVTV; WE43: 76.7 ± 13.1%; WE43-PEO: 73.1 ± 16.2%; p = 0.732). Intramedullar (BV/TV; WE43: 33.2 ± 16.7%; WE43-PEO 18.4 ± 9.0%; p = 0.047) and subperiosteal (bone area; WE43: 2.6 ± 3.4 mm2; WE43-PEO: 6,9 ± 5.2 mm2; p = 0.049) new bone formation was found for both, surface-modified and non-surface-modified groups. After twelve months, no significant differences of SV/TV and BV/TV were found between the two groups.PEO surface modification of WE43 plate systems improved osseointegration and significantly reduced the degradation rate within the first six months in vivo. Osteoconductive and osteogenic stimulation by WE43 magnesium implants led to overall increased bone growth, when prior PEO surface modification was conducted.

Validating scoring systems for fracture healing in infants and young children: pilot study

BackgroundRecent studies have analysed birth-related clavicular fractures to propose time frames for healing that could be applied to dating of all fractures in cases of suspected child abuse.ObjectiveTo assess differences in healing rates between femoral fractures and birth-related clavicular fractures in infants and young children.Materials and methodsA retrospective 5-year pilot study of femoral fractures in children younger than 3 years of age was performed. Anonymised radiographs were independently scored by two radiologists for stages of fracture healing. In cases of reader disagreement, radiographs were independently scored by a third radiologist.ResultsIn total, 74 radiographs (30 children) met the inclusion criteria. Fracture healing evolved over time with subperiosteal new bone formation (SPNBF) appearing first, followed by callus then remodelling. A power calculation for a single proportion, with a level of confidence of 95% and a margin of error of 5%, showed that in a definitive study, 359 radiographs would be required.ConclusionAlthough the overall pattern of healing is similar, in this small pilot study, the earliest times for SPNBF and callus formation in femoral fractures appeared to lag behind healing of birth-related clavicular fractures. Remodelling appeared earlier than remodelling of clavicular fractures. A power calculation has determined numbers of femoral radiographs (359) required for a definitive study.

COMPARISON BETWEEN LOW AND HIGH DOSES OF PROPHYLACTIC VITAMIN D IN PREVENTION OF OSTEOPENIA OF PREMATURITY

Osteopenia of prematurity (OOP) is a term used to describe a reduction in bone mineral content (BMC) of the preterm infant. Its incidence has been steadily increasing with the survival of more premature neonates as a result of advances in neonatal care. The prevalence of metabolic bone disease is inversely associated with birth weight and gestational age. Up to a third of infants weighing less than one kilogram at birth are osteopenic, more so if they are breastfed.To develop normally, the skeleton of the fetus requires active materno-fetal transfer of protein, Calcium (Ca) and phosphorus (P). Bone mineralization which occurs predominantly during the third trimester will be inadequate if the fetal increased demands in Ca and P are not met. During pregnancy augmented maternal intestinal absorption and increased skeletal mobilization increase maternal Ca supply to the fetus.Factors that impede normal bone mineralization include inadequate postnatal intake of vitamin D, calcium (Ca) and phosphorus (P), extended periods of total parenteral nutrition, and also as a side effect of diuretics and corticosteroids prescribed to these infants. Poor bone mineralization is associated with common neonatal conditions. These include sepsis, bronchopulmonary dysplasia, cerebral pathology, acidosis, necrotizing enterocolitis and cholestasis.Depending on the severity of the demineralization, osteopenia can remain clinically silent or, if severe, can cause bone changes in the form of rarefaction, fraying, cupping, subperiosteal new bone formation or even fractures.

ПАЛЕОПАТОЛОГИЧЕСКИЕ ИНДИКАТОРЫ «КАЧЕСТВА ЖИЗНИ» ДЕТЕЙ СРУБНОГО ВРЕМЕНИ ЮЖНОГО ПРИУРАЛЬЯ

This article presents results of paleopathological study of non-adult skeletons from three Srubnaya culture cemeteries (Karanaevskiy, Nikolaevskiy and Chumarovo-1) located in the southwest of the Republic of Bashkortostan. The analyzed sample includes skeletal remains of 41 individuals from burials dated to the 1600–1400 BC. In this study solely skeletal pathologies are discussed without dental pathologies. The following groups of pathologies were recorded: abnormal cortical porosities and subperiosteal new bone formation, endocranial lesions, traces of chronic sinusitis, mastoiditis and otitis media, as well as markers of “physical stress” (including skeletal traumas). This work attempts to assess the “quality of life” of the non-adult Srubnaya culture population of the Southern Ural. The sample is characterized by an underrepresentation of infants and young children and increased proportion of adolescents, indicating that the burial grounds were formed according to some socially selective principles. The studied group is characterized by the absence of macroscopical manifestations of specific infections and reliably diagnosable cases of scurvy or rickets. High frequencies of anemia markers (cribra orbitalia) and chronic maxillary sinusitis are likely indicative not of a maladaptation, but, on the contrary, of the good enough adaptation of the non-adults of the Srubnaya culture population to the environmental factors. Well expressed “physical stress” markers (cortical defects, osteochondritis dissecans and Schmorl’s nodes), observed for the studied osteological sample, suggest that children as young as 6–7 years old were likely involved in household activities.

Comparing Clinical and Radiographic Characteristics of Chronic Diffuse Sclerosing Osteomyelitis and Craniofacial Fibrous Dysplasia in the Mandible

Differential diagnosis of chronic diffuse sclerosing osteomyelitis of the mandible (DSOM) and craniofacial fibrous dysplasia (CFD) involving the mandible is challenging. The purpose of this study was to explore the differences of the clinical and radiographic characteristics between these 2 conditions. In this retrospective cross-sectional, blinded, comparative study, clinical and imaging data of patients with DSOM and CFD at the Peking University Hospital of Stomatology from 2012 to 2018 were retrieved. Clinical characteristics, mainly pain, swelling, and trismus, and radiographic findings, including sclerosis, lysis, and subperiosteal bone formation, were evaluated. The t test, χ2 test, and Fisher-Freeman-Halton test were used to determine differences. Thirty-seven patients with DSOM and 32 patients with CFD were included (mean ages, 24.2 and 28.4years, respectively); both groups showed a female predilection. DSOM (91.9%) and CFD (84.4%) were mainly unilateral. Patients with DSOM mainly presented with pain (94.6%), soft-tissue swelling (100.0%), and trismus (54.1%), whereas those with CFD did not experience pain (90.6%) and showed bone enlargement (87.5%) without trismus (6.3%). Panoramic radiographs and computed tomography scans of patients with DSOM showed subperiosteal bone formation, cortex lysis, and poorly demarcated cortex, whereas those patients with CFD mainly showed moderate-to-severe bone expansion, well-demarcated cortex, and tooth and mandibular canal displacement. These findings emphasize the importance of clinical and radiographic features in differentiating between DSOM and CFD. Pain, soft-tissue or bone-tissue swelling, subperiosteal bone formation, clarity of the boundary of the cortex and medulla, and continuity of the cortical bone are key points facilitating differentiation.

Feline Hypertrophic Osteopathy Associated with Congenital Megaesophagus: Two Case Reports and Literature Review

This report describes two cases of feline hypertrophic osteopathy (HO) associated with congenital megaesophagus (ME). The diagnosis was based upon case history, physical examination, radiography and laboratory investigations. The clinical signs of both cats included; regurgitation, weakness and reluctance to walk since birth. Physical examination revealed painful and thickened long bones, swollen joints, difficult flexion of all four limbs and normal urination, defecation, appetite as well as heart and respiratory rates. The abnormal laboratory findings were thrombocytosis, leukocytosis with lymphocytosis and monocytosis. Survey and contrast thoracic radiography showed generalizedesophageal dilatation. Radiography of appendicular skeleton revealed symmetrical and massive subperiosteal new bone formation of the affected long bones and pelvis. In conclusion, radiography of extremities is highly recommended for cats admitted with congenital ME and lameness to investigate the possibility of HO. Moreover, the HO should be listed duringthe differential diagnosis of thickened limbs in cats.

Osteogenic effects of bioabsorbable magnesium implant in rat mandibles and in vitro

Bone augmentation or grafting is often required for placement of dental implants or surgical reconstruction of bony defects. Bioabsorbable magnesium implant was shown to promote osteogenesis in long bones. The objectives of this study were to determine osteogenic effects of pure magnesium (Mg) in rat mandible and underlying mechanisms. Pure Mg was implanted in sockets after rat mandibular incisors were extracted. Titanium (Ti) was used as control. Systemic effects were determined by serum Mg level and histologic analyses of liver and kidney. Local Mg concentration was measured by microscopy-energy-dispersive spectroscopy (SEM-EDS). Alveolar bone was analyzed by micro-computed tomography (micro-CT) and histology. Osteogenic effects of 0.8 to 20mM magnesium chloride (MgCl2 ) on periosteum-derived cells (PDCs) were evaluated by proliferation, alizarin red staining and quantitative RT-PCR assays. Systemic effects were similar in Mg and Ti groups. Higher local Mg concentration was detected in Mg group (P<0.05). Micro-CT showed higher alveolar bone volume (2- and 6-weeks post-operation) and denser cancellous bone (2weeks post-operation) in Mg group, with significant amount of new subperiosteal bone formation on lateral alveolar bone surfaces by H&E staining. In PDC culture, proliferation rates, osteogenic gene expression for runt related transcription factor 2 (Runx2), bone sialoprotein (Bsp) and osteocalcin (Ocn), as well as calcium nodule formation rose significantly in 5, 10, and 20mM MgCl2 groups. Rapid osteogenesis (especially subperiosteal) is induced by pure Mg in rat mandibular alveolar bone. Osteogenic capacity of PDCs is enhanced by higher Mg ion concentrations in vitro.

Circulating Myostatin Levels Decrease Transiently after Implantation of a Hip Hemi-Arthroplasty

Introduction: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty. Methods: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury. Results: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery. Conclusions: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis.

Proximal femoral physeal fractures in children: a rare abusive injury.

Proximal femoral physeal fractures are rare in abused children. Recognition may be hampered due to their rarity and lack of an ossified femoral head. Prompt diagnosis and treatment are essential to preventing coxa vara. To demonstrate the radiographic features of proximal femoral physeal fractures both with unossified and ossified femoral heads. We reviewed our Institutional Review Board-approved 21-year radiology database of 2,206 children who had a skeletal survey as part of their medical evaluation for possible abuse. Cases of proximal femoral physeal fractures were identified. Eight patients, ages 2.5 to 26months, with 10 fractures were found, yielding a prevalence of 0.4% (8/2,206). In all fractures, there was lateral displacement of the proximal femur. In three fractures, the femoral head was not ossified, simulating a hip dislocation. The intra-articular location of the femoral head was verified by ultrasound or abdomen computed tomography. Subperiosteal new bone formation was present in six fractures, all non-weight-bearing patients. The femoral head was ossified in seven cases, all with medial rotation of the femoral head. Metaphyseal irregularity was present in three of four fractures of the weight-bearing patients; two of three also had metaphyseal scalloping resembling osteomyelitis. The three with metaphyseal irregularity developed coxa vara. Proximal femoral physeal fractures are rare in abuse cases. All present with lateral displacement of the proximal femur. With an unossified femoral head, it can simulate hip dislocation, which can be clarified with hip sonogram. Metaphyseal irregularity appears to be a feature in weight-bearing patients.

A carbon and nitrogen isotopic investigation of a case of probable infantile scurvy (6th–4th centuries BC, Slovenia)

This paper presents a case study of a young infant, from a larger isotopic and osteological investigation of Bronze/Iron Age (14th-4th century BCE) skeletal assemblages from Croatia and Slovenia. The osteological analysis of this infant identified pathological lesions including abnormal porosity and new bone formation consistent with malnutrition and phases of recovery. The distribution and appearance of these pathological lesions (i.e. diffuse micro-porosities and plaques of subperiosteal new bone formation on the skull and long bones) led to the conclusion that this infant probably suffered from scurvy (vitamin C deficiency). The diet and nitrogen balance of this individual were investigated by incremental dentine sampling and stable carbon and nitrogen isotope analysis. This sampling method provided a high resolution record of dietary and metabolic changes from pre-birth to around the time of death. The resulting isotope data exhibited unusually high δ13C values for this region and time period (between −11.3‰ and −12.6‰), while δ15N values were observed to be c. 3‰ above that of rib collagen sampled from contemporary adults recovered from the same site. The isotope profiles generated from the incremental dentine analysis show that δ13C and especially δ15N continue to increase until death. The evidence from the skeletal remains and high resolution isotopic data support the hypothesis that this infant suffered from severe malnutrition and an increasingly negative nitrogen balance. The paper discusses some scenarios which could have resulted in these unusual isotope ratios, whilst considering the diagnosis of possible metabolic disease. The paper also addresses the need for context when interpreting isotopic results. The isotope data should not be viewed in isolation, but rather as part of a multidisciplinary approach, considering the multiple causes of isotopic variability.

Establishing signs for acute and healing phases of distal tibial classic metaphyseal lesions.

Stages of healing for classic metaphyseal lesions (CMLs) are not well established. Follow-up skeletal surveys provide an opportunity to evaluate signs of healing CMLs. To evaluate the sequence of CML healing phases by comparing initial and follow-up skeletal surveys in children with distal tibial CMLs on the initial survey. Findings could assist in child abuse investigations. We identified all distal tibia CMLs with initial and follow-up skeletal surveys performed January 2009 through December 2018 at our institution. Two pediatric radiologists reviewed the surveys using Likert score from 1 (no CML) to 5 (definite CML). Only cases with score of 4 or 5 by both radiologists were selected for the study. The initial and 2-week follow-up skeletal surveys were reviewed in consensus for presence of the following signs: corner fracture, thin bucket handle fracture, thick bucket handle fracture, bucket handle fracture with endochondral bone filling the gap, subphyseal lucency, deformed corner, and subperiosteal new bone formation. We used the Kruskal-Wallis test to evaluate for significant difference in thickness among thin bucket handle fracture, thick bucket handle fracture, and bucket handle fracture with endochondral bone filling the gap. We included 26 children (12 girls) with age range 1-9.9months who had a combined 34 distal tibia CMLs. Thin bucket handle fracture (n=13, 38.2%) was only seen on initial survey. On follow-up, six children had thick bucket handle fracture and four had bucket handle fracture with endochondral bone filling the gap. Fourteen thick bucket handle fractures (n=9) or bucket handle fractures with endochondral bone filling the gap (n=5) were noted on initial surveys; on follow-up, three (21.4%) had deformed corner, one (7.1%) had corner fracture, one (7.1%) had subphyseal lucency, and five (35.7%) were normal. None demonstrated thin bucket handle fracture on follow-up. Two of the nine (22.2%) thick bucket handle fractures became thicker, and 3/9 (33.3%) became bucket handle fractures with endochondral bone filling the gap. The metaphysis normalized in 8/34 (23.5%) CMLs on follow-up surveys. The thickness of thin bucket handle fracture was less than 1mm (mean±standard deviation [SD] = 0.6±0.2mm), which was significantly thinner (P<0.0001) compared with thick bucket handle fracture (1.7±0.5mm) and bucket handle fracture with endochondral bone filling the gap (1.9±0.6mm). The lack of thin bucket handle fractures on any follow-up skeletal surveys suggests this sign represents an acute phase of injury. The next phases of healing appear to be thick bucket handle fracture followed by bucket handle fracture with endochondral bone filling the gap. It is important to note that normalization of the metaphysis at 2-week follow-up does not exclude CML because this was seen in about one-fifth of cases.

Radiographic overlap of recurrent Caffey disease and chronic recurrent multifocal osteomyelitis (CRMO) with considerations of molecular origins.

Caffey disease, or infantile cortical hyperostosis, classically describes a self-limited inflammatory disorder that presents in the infant with fussiness, focal swelling and sometimes fever. Imaging is conventionally limited to radiography, which shows mild to profound subperiosteal bone formation and sometimes deformity. This disease was not uncommonly diagnosed in the late 20th century. Interestingly, the disease may not just occur in the infant, and it may be due to a genetic mutation in the alpha-one chain of type 1 collagen (COL1A1). Recurrent or delayed onset in the older child or adolescent also occurs. In more recent years, another type of inflammatory bone disorder, chronic sterile osteomyelitis, has been frequently recognized and, depending on the radiographic stage or the diagnostic modality used, may have characteristics overlapping with Caffey disease. In this review, we discuss the demographics, imaging and known etiologies for Caffey disease and chronic recurrent multifocal osteomyelitis and raise the possibility of similar molecular origins.

A comparison of the cone beam computed tomography findings in medication-related osteonecrosis of the jaws related to denosumab versus bisphosphonates: an observational pilot study.

The aim of this study was to compare the radiographic abnormalities on cone beam computed tomography (CBCT) in patients with medication-related osteonecrosis of the jaws (MRONJ) related to denosumab use versus bisphosphonate use. The study included 34 consecutive patients with MRONJ who had a history of exclusive use of denosumab (n = 17) or bisphosphonates (n = 17) and had undergone CBCT for determination of extent of disease. Demographic data of the patients were collected. Differences in radiologic characteristics between patients with denosumab-related osteonecrosis of the jaws (DRONJ) and those with bisphosphonate-related osteonecrosis of the jaws (BRONJ) were scored and studied on CBCT. In patients with DRONJ, sequestra (P = .015) and lysis of the cortical border of the jaw (P = .033) were significantly less common than in patients with BRONJ. Subperiosteal bone formation did not differ between the groups (P = .545). There was no association between stage of disease and duration of drug therapy or duration of symptoms for either medication group. The radiologic features of DRONJ may be different from those of BRONJ with regard to the presence of sequestra and cortical lysis and might, therefore, be improperly diagnosed. Underestimation and undertreatment of DRONJ may potentially lead to progression of disease and, thus, make treatment more difficult.

Microcomputed tomography and genetic analysis of a rare case of Caffey's disease in a 5–7‐month‐old girl

AbstractAncient human remains provided precious information about the health and disease of individuals from the past. Usually, diagnosis and assessment of the paleopathological remains were performed using RX analysis, tomography, and histology. However, thanks to the progress in ancient DNA recovery and sequencing, genetic information can used to support the diagnoses performed using classical approach. Here, we described the paleopathological remains of a 5 to 7‐month infant, excavated from Saint‐Jacques church (Douai, France), dated from 16th to 18th century. The skeleton displayed bone lesions, consisting in a massive corticoperiosteal thickening with subperiosteal new bone formation. To investigate the pathological condition of the remains, we applied a combined approach using both microcomputed tomography and paleogenetic analysis. Among several pathologies, we proposed a potential diagnosis of Caffey's disease (Infantile Cortical Hyperostosis, ICH), a rare genetic infantile pathology that causes a massive subperiosteal new bone formation in some diagnostic skeletal districts. Association of the disease with the COL1A1 gene on chromosome 17q21 has been highlighted in several familial cases, whereas other evidences suggest genetic heterogeneity of ICH. Although the osteological clinical picture was compatible with Caffey's disease, we did not find evidence of the mutated allele in COL1A1 gene, suggesting a diagnosis of ICH caused by a different genetic mutation. Our study represents one of the first documented historical case of Caffey's disease and highlights the contribution of paleopathological studies for a better knowledge of human diseases.

Subperiosteal new bone formation with the distal tibial classic metaphyseal lesion: prevalence on radiographic skeletal surveys.

The classic metaphyseal lesion (CML) is a strong indicator of infant abuse, and the distal tibia is one of the most common sites for this injury. To determine the prevalence of subperiosteal new bone formation accompanying the distal tibial CMLs identified on infant skeletal surveys. Skeletal surveys performed for suspected infant abuse (2005-2017) were reviewed. Inclusion criteria were 1) anteroposterior (AP) and lateral radiographs of a distal tibial CML from the initial survey, 2) AP radiograph from the 2-week follow-up survey, 3) additional fractures, 4) child protection team consults and 5) mandated report filing for suspected abuse. We identified 22 distal tibial CMLs from 16 infants. Radiographs of these lesions were shown on the picture archiving and communication system to two blinded pediatric radiologists. Readers indicated the presence/absence of subperiosteal new bone formation on individual and combinations of images. Inter-reader agreements were fair (kappa=0.47). The prevalence of subperiosteal new bone formation on initial AP radiograph was 34%. Significant increases in the prevalence were found with the addition of follow-up AP radiograph (57%; P<0.001), initial lateral radiograph (57%; P=0.002) and follow-up AP plus initial lateral radiographs (71%; P<0.001). Statistically significant increases in prevalence were also noted when the third view was added to the other two views (increase of 14%; P=0.024). Even when skeletal surveys include initial AP, lateral and follow-up AP radiographs of the tibia, nearly one-third of distal tibial CMLs will fail to demonstrate subperiosteal new bone formation.