A skeleton in a huff: insights in etiologies of osteosclerosis.

A 30-yr-old man developed right lower leg pain and a palpable solid mass. Radiographic imaging revealed a periosteal reaction with an exostotic mass arising from the right distal fibula. Generalized skeletal osteosclerosis with periosteal reaction was discovered on a radiographic skeletal survey. A biopsy of the right fibular mass revealed reactive woven bone. The patient was referred to a metabolic bone disease clinic, where laboratory values were consistent with secondary hyperparathyroidism and increased bone turnover. A DXA bone density scan revealed high bone density, with an L1-4 spine Z-score of +9.3, a left femoral neck Z-score of +8.5, and a total hip Z-score of +6.5. A dental exam revealed generalized gingival inflammation, teeth mobility, generalized horizontal alveolar bone loss and widening of the periodontal ligament space, increased bone density around the teeth, and thickening of the radicular lamina dura. An extensive evaluation was performed, with the result of a single test revealing the diagnosis. The differential diagnoses of osteosclerosis affecting the skeleton, teeth, and oral cavity are discussed.

A 30-yr-old man developed, over a short period, pain in his lower right leg accompanied by a hard mass. He also reported weight loss and night sweats for the past 6 months. After evaluation by his primary physician, an X-ray was ordered that reported a bony mass arising from the right fibula bone. A biopsy was performed of the mass, but no evidence of cancer or any other specific abnormality was found. The patient was then referred to a bone disease specialty clinic. Laboratory tests revealed a large increase in how quickly the patient's skeleton was remodeling, affecting the balance of bone formation and removal involved in maintaining a healthy skeleton. A bone density scan reported that the patient had very dense bones. Other unusual changes were also discovered in a dental exam, suggesting bone thickening. After an extensive evaluation, a single blood test revealed the cause of the fibular bone mass and dense bones.

Case Report: Osteosclerotic metaphyseal dysplasia with optic nerve involvement and progressive osteonecrosis of the jaw due to a novel LRRK1 mutation.

Background: Osteosclerotic metaphyseal dysplasia (OSMD, OMIM 615198) is an extremely rare autosomal recessive osteopetrosis disorder resulting in a distinctive pattern of osteosclerosis of the metaphyseal margins of long tubular bones. To date, only thirteen cases have been reported (eight molecularly confirmed). Five homozygous sequence variants in the leucine-rich repeat kinase 1 (LRRK1) gene have been identified to cause OSMD. We present two male siblings with OSMD with a novel LRRK1 variant. Cases: The index case, now aged 6 years, was referred aged 9 months when diffuse sclerosis of the ribs and vertebral bodies, suggestive of osteopetrosis, was incidentally identified on a chest radiograph for suspected lower respiratory tract infection. Parents were consanguineous and of Pakistani origin. Further evaluation revealed developmental delay, nystagmus with bilateral optic nerve hypoplasia and severe visual impairment. Skeletal survey confirmed typical changes of OSMD, with widespread diffuse sclerosis and Erlenmeyer flask deformity of long bones. His older sibling, now aged 12 years, was 7 years at the time of referral and had similar clinical course and skeletal findings. Additionally, he had a chronic progressive osteonecrosis of the left mandible that required debridement, debulking and long-term antibiotics. Skeletal survey revealed findings similar to his sibling. Neither sibling had significant skeletal fractures or seizures. Unlike most previous reports suggesting sparing of the skull and lack of visual impairment, our patients had evidence of osteosclerosis of the cranium. Genetic screening for the common autosomal recessive and dominant pathogenic variants of osteopetrosis was negative. Whole Exome Sequencing (WES) followed by Sanger sequencing, identified a novel homozygous LRRK1 c.2506C>T p. (Gln836Ter) nonsense variant predicted to result in premature truncation of LRRK1 transcript. Conclusion: Our cases confirm the autosomal recessive inheritance and expand the spectrum of genotype and phenotype of OSMD reported in the literature. Increasing reports of LRRK1 variants in this phenotype raise the question of whether LRRK1 should be included in targeted osteopetrosis panels. Bone histology in previous cases has shown this to be an osteoclast rich form of osteopetrosis raising the possibility that haematopoietic stem cell transplantation may be an appropriate treatment modality.

Mutations of family with sequence similarity 20-member C gene causing lethal and nonlethal Raine syndrome causes hypophosphatemia rickets.

Family with sequence similarity 20-member C (FAM20C) is a kinase specific to most of the secreted phosphoproteome. FAM20C has been identified as the causative gene of Raine syndrome, initially characterized by lethal osteosclerosis bone dysplasia. However, since the identification of the cases of nonlethal Raine syndrome characterized by hypophosphatemia rickets, the previous definition of Raine syndrome has become debatable and raised a question about the role of mutations of FAM20C in controversial skeletal manifestation in the two forms of the disease. In this study, we aimed to investigate the influence of FAM20C mutations on skeletogenesis. We developed transgenic mice expressing Fam20c mutations mimicking those associated with human lethal and nonlethal Raine syndrome. The results revealed that transgenic mice expressing the mutant Fam20c found in the lethal (KO;G374R) and nonlethal (KO;D446N) Raine syndrome exhibited osteomalacia without osteosclerotic features. Additionally, both mutants significantly increased the expression of the Fgf23, indicating that Fam20c deficiency in skeletal compartments causes hypophosphatemia rickets. Furthermore, as FAM20C kinase activity catalyzes the phosphorylation of secreted proteomes other than those in the skeletal system, global FAM20C deficiency may trigger alterations in other systems resulting in osteosclerosis secondary to hypophosphatemia rickets. Together, the findings of this study suggest that FAM20C deficiency primarily causes hypophosphatemia rickets or osteomalacia; however, the heterogeneous skeletal manifestation in Raine syndrome was not determined solely by specific mutations of FAM20C. The findings also implicated that rickets or osteomalacia caused by FAM20C deficiency would deteriorate into osteosclerosis by the defects from other systems or environmental impacts.

Hepatitis C-associated Osteosclerosis (HCAO): Long-Term Follow-Up of a New Case Recovered After Antiviral Treatment.

Hepatitis C-associated osteosclerosis (HCAO) is a very rare condition that can be observed in a small number of patients with Hepatitis C Virus (HCV) infection. HCAO is usually characterized by widespread bone sclerosis, associated with severe bone pain, and increased levels of bone turnover markers, especially alkaline phosphatase (ALP). In this report, we present the case of a 55-year-old woman who was affected by HCV and came to our attention for severe and diffuse bone pain. Radiological studies showed bone sclerosis, and bone mineral density (BMD) was markedly increased, as well as serum ALP levels. The patient was initially treated with intravenous pamidronate, which provided only a transient benefit on clinical symptoms. Then antiviral therapy for HCV (interferon-alfa and ribavirin) was started and it was effective in making the viral load undetectable. After a long follow-up period, we observed a persistent remission of bone pain, a reduction in BMD together with a progressive trend toward the normalization of bone turnover markers. In conclusion, HCAO, although rare, should be considered among the potential causes of increased bone mass in patients with HCV infection, and treatment for the underlying infection may be effective in controlling the manifestations of this disease.

Bone and Cytokine Markers Associated With Bone Disease in Systemic Mastocytosis.

BACKGROUND: Mastocytosis encompasses a heterogeneous group of diseases characterized by tissue accumulation of clonal mast cells, which frequently includes bone involvement. Several cytokines have been shown to play a role in the pathogenesis of bone mass loss in systemic mastocytosis (SM), but their role in SM-associated osteosclerosis remains unknown. OBJECTIVE: To investigate the potential association between cytokine and bone remodeling markers with bone disease in SM, aiming at identifying biomarker profiles associated with bone loss and/or osteosclerosis. METHODS: A total of 120 adult patients with SM, divided into 3 age and sex-matched groups according to their bone status were studied: (1) healthy bone (n = 46), (2) significant bone loss (n = 47), and (3) diffuse bone sclerosis (n = 27). Plasma levels of cytokines and serum baseline tryptase and bone turnover marker levels were measured at diagnosis. RESULTS: Bone loss was associated with significantly higher levels of serum baseline tryptase (P = .01), IFN-γ (P = .05), IL-1ß (P = .05), and IL-6 (P = .05) versus those found in patients with healthy bone. In contrast, patients with diffuse bone sclerosis showed significantly higher levels of serum baseline tryptase (P < .001), C-terminal telopeptide (P < .001), amino-terminal propeptide of type I procollagen (P < .001), osteocalcin (P < .001), bone alkaline phosphatase (P < .001), osteopontin (P < .01), and the C-C Motif Chemokine Ligand 5/RANTES chemokine (P = .01), together with lower IFN-γ (P = .03) and RANK-ligand (P = .04) plasma levels versus healthy bone cases. CONCLUSIONS: SM with bone mass loss is associated with a proinflammatory cytokine profile in plasma, whereas diffuse bone sclerosis shows increased serum/plasma levels of biomarkers related to bone formation and turnover, in association with an immunosuppressive cytokine secretion profile.

Osteopathia striata with cranial sclerosis causing a compressive optic neuropathy.

BACKGROUND: Osteopathia striata combined with cranial sclerosis (OS-CS) is an inherited skeletal dysplasia that manifests with macrocephaly, orofacial abnormalities, thickened craniofacial bones, and vertically oriented radiodensities of the long bones. CASE REPORT: Here, we present a severe case of OS-CS in a 4-year-old girl causing optic neuropathy as shown by radiographic evidence, ophthalmic findings, and histopathology. Previous genetic testing in this patient revealed a de novo heterozygous mutation in AMER1 (c.1057C>T, p.Arg353Ter). Although the patient had a pre-existing, appropriately functioning, ventriculoperitoneal (VP) shunt, a subsequent MRI of the brain and orbits showed narrowing of the bilateral optic nerve canals secondary to osseous thickening causing bilateral optic nerve atrophy, worse on the left. The patient underwent staged bilateral orbital osteotomies, optic canal decompression, and bilateral frontal craniotomy, and at 11 months postoperatively, her vision remained stable. Conclusions: While up to 50% of the patients with OS-CS may experience hearing loss due to cranial nerve compression, we present a case of severe visual loss secondary to OS-CS-associated optic nerve compression.

Partial Claviculectomy to Relieve Tracheal Compression in an Adult Male with Osteomesopyknosis.

BACKGROUND: The clavicle is a long bone that forms the anterior border of the thoracic inlet. Anatomic abnormalities of the clavicle can lead to compression of the innominate artery and trachea due to mass effect. These anatomic abnormalities can be amenable to surgical resection, which can provide complete resolution of symptoms. METHODS: We present a case of tracheal compression by the innominate artery in an adult man, caused by a clavicular abnormality due to an underlying bone mineralization disorder, corrected by partial resection of the right clavicle. RESULTS: The patient underwent successful open surgical resection of his right clavicular head leading to resolution of his tracheal compression by the innominate artery. CONCLUSIONS: We believe that this is the first description of tracheal compression due to osteomesopyknosis. This case demonstrates that compression of the innominate artery due to a clavicular abnormality can be safely corrected via open surgical resection.

Wilms tumor in patients with osteopathia striata with cranial sclerosis.

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Somatically acquired variants in AMER1 are found in neoplastic tissue in 15-30% of patients with Wilms tumor; however, to date, only one individual with OSCS has been reported with a Wilms tumor. Here we present four cases of Wilms tumor in unrelated individuals with OSCS, including the single previously published case. We also report the first case of bilateral Wilms tumor in a patient with OSCS. Tumor tissue analysis showed no clear pattern of histological subtypes. In Beckwith-Wiedemann syndrome, which has a known predisposition to Wilms tumor development, clinical protocols have been developed for tumor surveillance. In the absence of further evidence, we propose a similar protocol for patients with OSCS to be instituted as an initial precautionary approach to tumor surveillance. Further evidence is needed to refine this protocol and to evaluate the possibility of development of other neoplasms later in life, in patients with OSCS.

A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age.

Raine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-a-bone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed.

Insulin-like growth factor-II and bioactive proteins containing a part of the E-domain of pro-insulin-like growth factor-II.

Insulin-like growth factor (IGF)-II is considered to function as an important fetal growth factor, which is structurally and functionally related to IGF-I and proinsulin. At least in vitro, IGF-II actions are mediated through the IGF-I receptor and to a lesser extent the insulin receptor. After birth, the function of IGF-II is less clear although in adults the serum level of IGF-II exceeds that of IGF-I several fold. The IGF-II gene is maternally imprinted, with exception of the liver and several parts of the brain, where it is expressed from both alleles. The regulation, organization, and translation of the IGF-II gene is complex, with five different putative promotors leading to a range of noncoding and coding mRNAs. The 180-amino acid pre-pro-IGF-II translation product can be divided into five domains and include a N-terminal signal peptide of 24 amino acid residues, the 67 amino acid long mature protein, and an 89 residues extension at the COOH terminus, designated as the E-domain. After removal of the signal peptide, the processing of pro-IGF-II into mature IGF-II requires various steps including glycosylation of the E-domain followed by the action of endo-proteases. Several of these processing intermediates can be found in the human circulation. There is increasing evidence that, besides IGF-II, several incompletely processed precursor forms of the protein, and even a 34-amino acid peptide (preptin) derived from the E-domain of pro-IGF-II, exhibit distinct biological activities. This review will focus on the current insights regarding the specific roles of the latter proteins in cancer, glucose homeostasis, and bone physiology. To address this topic clearly in the right context, a concise overview of the biological and biochemical properties of IGF-II and several relevant aspects of the IGF system will be provided.

Intra-medullary osteosclerosis of the tibia in children.

BACKGROUND: Intra-medullary osteosclerosis of the tibia is a rare condition characterised by chronic pain due to diaphyseal hyperostosis with no detectable triggering factor. The main differential diagnoses are stress fracture and osteoid osteoma. Of the few cases reported to date, most were in adults. The objective of this study was to assess paediatric patients with intra-medullary osteosclerosis to determine whether the first visit provides sufficient information to establish the diagnosis and rule out both osteoid osteoma and stress fracture, whether a biopsy is required, and which treatment is optimal. HYPOTHESIS: The diagnosis of intra-medullary osteosclerosis of the tibia can be made at the first visit. PATIENTS AND METHODS: Seven paediatric patients, 4 males and 3 females, with a mean age of 11 years, were included in this retrospective study. We evaluated the clinical features, findings from imaging studies (standard radiographs, computed tomography, magnetic resonance imaging, and bone scintigraphy), and treatment outcomes. RESULTS: At the first visit, all patients had a painful swelling at the middle of the shin and imaging study evidence of antero-lateral tibial cortical thickening extending into the medullary cavity; in 5 patients, a linear lucency was visible. No other bone abnormalities were seen. Treatments included non-operative measures, pinning, and nailing. None of these treatments provided permanent bone healing or pain relief, although transitory freedom from pain with or without radiological bone healing was achieved. DISCUSSION: Intra-medullary osteosclerosis of the tibia is rarely reported and therefore probably underdiagnosed. Distinctive characteristics of the cortical and endosteal thickening include location at the antero-lateral mid-diaphysis and, in some cases, the concomitant presence of a linear lucency that can provide the early diagnosis. The distinctive radiological features allow differentiation from a stress fracture. The management is challenging. LEVEL OF EVIDENCE: IV, retrospective observational study.

Unique Variant of NOD2 Pediatric Granulomatous Arthritis With Severe 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia and Generalized Osteosclerosis.

Pediatric granulomatous arthritis (PGA) refers to two formerly separate entities: autosomal dominant Blau syndrome (BS) and its sporadic phenocopy early-onset sarcoidosis (EOS). In 2001 BS and in 2005 EOS became explained by heterozygous mutations within the gene that encodes nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also called caspase recruitment domain-containing protein 15 (CARD15). NOD2 is a microbe sensor in leukocyte cytosol that activates and regulates inflammation. PGA is characterized by a triad of autoinflammatory problems (dermatitis, uveitis, and arthritis) in early childhood, which suggests the causal NOD2/CARD15 mutations are activating defects. Additional complications of PGA were recognized especially when NOD2 mutation analysis became generally available. However, in PGA, hypercalcemia is only briefly mentioned, and generalized osteosclerosis is not reported, although NOD2 regulates NF-κB signaling essential for osteoclastogenesis and osteoclast function. Herein, we report a 4-year-old girl with PGA uniquely complicated by severe 1,25(OH)2 D-mediated hypercalcemia, nephrocalcinosis, and compromised renal function together with radiological and histopathological features of osteopetrosis (OPT). The classic triad of PGA complications was absent, although joint pain and an antalgic gait accompanied wrist, knee, and ankle swelling and soft non-tender masses over her hands, knees, and feet. MRI revealed tenosynovitis in her hands and suprapatellar effusions. Synovial biopsy demonstrated reactive synovitis without granulomas. Spontaneous resolution of metaphyseal osteosclerosis occurred while biochemical markers indicated active bone turnover. Anti-inflammatory medications suppressed circulating 1,25(OH)2 D, corrected the hypercalcemia, and improved her renal function, joint pain and swelling, and gait. Mutation analysis excluded idiopathic infantile hypercalcemia, type 1, and known forms of OPT, and identified a heterozygous germline missense mutation in NOD2 common in PGA (c.1001G>A, p.Arg334Gln). Thus, radiological and histological findings of OPT and severe hypercalcemia from apparent extrarenal production of 1,25(OH)2 D can complicate NOD2-associated PGA. Although the skeletal findings seem inconsequential, treatment of the hypercalcemia is crucial to protect the kidneys. © 2018 American Society for Bone and Mineral Research.

Tracking the Progression of Osteolytic and Osteosclerotic Lesions in Mice Using Serial In Vivo µCT: Applications to the Assessment of Bisphosphonate Treatment Efficacy.

The metastasis of tumor cells to bone can lead to osteolytic and osteosclerotic lesions, which cause severe, highly-localized bone destruction and abnormal bone apposition, respectively. Accurate quantification of lesion progression is critical to understand underlying mechanisms and assess treatment efficacy; however, standard structural parameters may be insensitive to local changes. We developed methods to quantify osteolytic and osteosclerotic lesions using micro-computed tomography (µCT) within in vivo mouse datasets. Two Balb/c nude datasets were used: (i) bone-homing MDA-MB-231 (osteolytic) cells injected into the left ventricle, treatment with alendronate or vehicle, and weekly µCT (proximal tibia) for 4 weeks, and (ii) MCF7 (osteosclerotic) cells injected into the right tibia and weekly µCT over 12 weeks. After registering images to baseline, osteolytic lesion volume was determined by summing all baseline bone voxels at distances greater than a threshold (150 µm) from the nearest follow-up. Osteosclerotic lesions were determined by measuring the distance from each follow-up surface voxel to the nearest baseline surface and calculating the standard deviation of distance values (SDDT) of the surrounding voxels. Bone mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were determined for comparison. Osteolytic lesions were observed 1 week after tumor cell injection; however, no corresponding BV/TV losses or Sp increases were observed, indicating that standard parameters were unable to detect early metastatic changes. Lesion volume was smaller in the alendronate versus control group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at weeks 3 and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed following injection, providing a potential new measure of osteosclerotic bone apposition. These data show that quantification of local structural change with serial µCT may overcome the limitations of standard mineral and microstructural parameters, and successfully separates metastatic and normal bone turnover. © 2017 American Society for Bone and Mineral Research.

Multiple Osteosclerotic Lesions: ARare Presentation of Hyperparathyroidism Secondary to Hypovitaminosis D.

Hypovitaminosis D is an under-recongnised and important factor responsible for secondary hyperparathyroidism. Hyperparathyroidism mostly presents with osteolytic lesions, especially in secondary hyperparathyroidism with renal failure. There are some rare presentations of hyperparathyroidism as focal or generalized osteosclerotic lesions. The exact mechanism for the osteosclerosis is still unknown, but there are some theories suggesting an exaggerated response of osteoblasts in response to prolonged osteolytic activity in order to restore bone loss. Here, we report a case of secondary hyperparathyroidism secondary to severe Vitamin D deficiency presented as multiple osteosclerotic lesions.

Painful neuropathy caused by compression of the inferior alveolar nerve by focal osteosclerotic lesion of the mandible: A case report.

Osteosclerotic lesions are a common finding on dental radiographs. They are considered developmental variants of a normal bone architecture and they usually do not need any treatment. The purpose of this article is to present a rare case of osteosclerotic lesion of the mandible causing trigeminal neuropathy by compression of the alveolar nerve. The pain started with dental hypersensitivity of the mandibular right first molar. Later on, signs of irreversible molar tooth pulpitis developed. Endodontic therapy and apicoectomy did not resolve the pain, which later intensified, and painful neuropathy localized to inferior alveolar nerve developed; therefore, surgical decompression was indicated. Treating a dental patient with neuralgic pain is always a challenge, especially if there is no obvious source or reason for this type of pain. A clear evaluation and treatment protocol are important to minimize the patient's morbidity and avoid unnecessary overtreatment.

A Novel ANO5 Mutation Causing Gnathodiaphyseal Dysplasia With High Bone Turnover Osteosclerosis.

Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome that involves an osteopetrosis-like sclerosis of the long bones and fibrous dysplasia-like cemento-osseous lesions of the jawbone. Although the genetic analysis of the respective patients has revealed mutations in the ANO5 gene as an underlying cause, there is still no established consensus regarding the bone status of GDD patients. We report a new case of GDD in a 13-year-old boy with recurrent diaphyseal fractures of the femur, in whom we identified a novel de novo missense mutation in the ANO5 gene, causing a p.Ser500Phe substitution at the protein level. After confirming the presence of GDD-characteristic abnormalities within the jaw bones, we focused on a full osteologic assessment using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses. We thereby identified increased trabecular bone mass accompanied by elevated serum markers of bone formation and bone resorption. The high turnover bone pathology was further confirmed through the analysis of an iliac crest biopsy, where osteoblast and osteoclast indices were remarkably increased. Taken together, our findings provide evidence for a critical and generalized role of anoctamin-5 (the protein encoded by the ANO5 gene) in skeletal biology. As it is reasonable to speculate that modifying the function of anoctamin-5 might be useful for therapeutically activating bone remodeling, it is now required to analyze its function at a molecular level, for instance in mouse models. © 2016 American Society for Bone and Mineral Research.

Osteopathia striata with cranial sclerosis (OSCS): review of the literature and case report demonstrating challenges of spinal fusion after trauma.

Osteopathia striata with cranial sclerosis (OSCS) is a rare but well-described pathology characterized by abnormalities in bone deposition in the axial and cranial skeleton as well as other abnormalities and associated deficits. These skeletal abnormalities can lead to significant intra-operative challenges for the surgeon and influence outcomes for the patient. In this report, we present a case of a patient with OSCS who was involved in a traumatic motor vehicle crash and underwent posterior cervico-thoracic fusion for a T4 chance fracture. Bony abnormalities in the cervico-thoracic spine presented a significant operative challenge due to alterations in bony anatomy and bone architecture. This case serves as an example of the challenges that the spine surgeon faces when dealing with OSCS, and highlights the differences between OSCS and commoner skeletal hyperplasias such as osteopetrosis.