Osteosclerosis

IBIDS is a syndrome characterized by ichthyosis, brittle hair, impaired intelligence, decreased fertility, and short stature, but unassociated with skeletal lesions. This condition is considered a form of trichothiodystrophy because hair from several cases has been found to have a low sulfur content. We describe a 9-year and 10-month-old white boy whose clinical features resemble the IBIDS syndrome (ichthyosis, brittle hair, cataracts, and short stature), but who also has marked axial osteosclerosis and peripheral osteopenia. No abnormalities of mineral homeostasis were noted. Histopathologic assessment of nondecalcified bone specimens excluded osteopetrosis, but suggested slow skeletal remodeling. When subjected to polarized light microscopy, his hair exhibited the band-like pattern of birefringence described in trichothiodystrophy. Literature review disclosed 8 patients, 2 of whom had been diagnosed as trichothiodystrophy, with like clinical features including osteosclerosis. These skeletal abnormalities together with clinical features of the IBIDS/trichiodystrophy syndrome, we believe, reflect the prototype of a disorder that seems best described as central osteosclerosis with ectodermal dysplasia.

We describe a new familial metabolic bone disease characterized by expanding hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia. The condition affects a mother and daughter studied at the age of 36 years and 11 years, respectively. Both individuals lost all hearing in early childhood and suffered premature shedding of teeth. Skeletal pains began just before puberty. Swelling and aching of most middle phalanges in the hands is an especially troublesome manifestation. The mother also had episodes of symptomatic hypercalcemia first documented in late childhood and subsequently during intercurrent illness and postpartum lactation. Radiographs show hyperostosis and/or osteosclerosis predominantly in the skull and appendicular skeleton. Long bones also are expanded considerably, especially the middle phalanges in the fingers. The mother's skeletal abnormalities are more severe. Biochemical parameters of bone turnover, including serum alkaline phosphatase (ALP) activity, are elevated substantially. In the proposita, dynamic histomorphometry of nondecalcified sections of iliac crest revealed rapid skeletal remodeling. In the mother, who had been treated with bisphosphonates, electron microscopy (EM) showed disorganized collagen bundles as well as necrotic and apoptotic bone cells but no osteocytic osteolysis. Measles virus gene transcripts were not detected in peripheral blood monocytes. Karyotyping was normal, 46,XX. Hyperphosphatasia with bone disease previously has been reported as either a sporadic or autosomal recessive condition. Expansile skeletal hyperphosphatasia (ESH) is probably inherited as an autosomal dominant trait with a high degree of penetrance. (J Bone Miner Res 2000;15:2330 -2344)

Skeletal lesions are a frequent complication of breast and prostate cancer and a hallmark of multiple myeloma. Endocrine and paracrine factors modulate various aspects of bone metastases, including tumour proliferation, skeletal susceptibility to tumour homing, the microenvironment needed to support tumour persistence, and the initiation of a vicious cycle between tumour and bone-resident cells that further promotes tumour growth. Endocrine changes, such as oestrogen or vitamin D deficiency, contribute to a fertile bone microenvironment that might promote bone metastases. Bone health could be impaired further by existing cancer treatments, especially sex hormone deprivation. In this Review, we discuss the effect of hormones and associated local factors on cross-talk between bone metabolism and tumour biology. We review the biology of osteolytic and osteosclerotic lesions, with a focus on endocrine aspects, and outline potential therapeutic targets. We also summarise endocrine aspect...

Asian pongids (orangutans) and African hominids (gorillas, chimpanzees and humans) split 14-10 million years ago, possibly in the Middle East, or elsewhere in Eurasia, where the great ape fossils of 12-8 million years ago display pongid and/or hominid features. In any case, it is likely that the ancestors of the African apes, australopithecines and humans, lived on the Arabian-African continent 8-6 million years ago, when they split into gorillas and humans-chimpanzees. They could have frequently waded bipedally, like mangrove proboscis monkeys, in the mangrove forests between Eurasia and Africa, and partly fed on hard-shelled fruits and oysters like mangrove capuchin monkeys: thick enamel plus stone tool use is typically seen in capuchins, hominids and sea otters.
The australopithecines might have entered the African inland along rivers and lakes. Their dentition suggests they ate mostly fruits, hard grass-like plants, and aquatic herbaceous vegetation (AHV). The fossil data indicates that the early australopithecines of 4-3 million years ago lived in waterside forests or woodlands; and their larger, robust relatives of 2-1 million years ago in generally more open milieus near marshes and reedbeds, where they could have waded bipedally. Some anthropologists believe the present-day African apes evolved from australopithecine-like ancestors, which would imply that knuckle-walking gorillas and chimpanzees evolved in parallel from wading-climbing ‘aquarborealists’.
After the human-chimp split some 6-4 million years ago, our ancestors could have stayed at, or returned to the Indian Ocean shores, where they elaborated their shellfish-eating, tool-using, beach-combing and wading-diving skills. From here the different Homo species could have colonized Africa and Eurasia by following the rivers as bipedal omnivores. Homo erectus crossed Wallace’s Line and reached Flores before 0.8 million years ago, and the earliest erectus fossils are found in beaches and swamps from Java to Georgia and Kenya 1.8-1.6 million years ago. Voluntary breath-holding, an essential requirement for diving, probably facilitated the evolution of human speech.

Objective: To review the imaging findings, age and gender distribution of chondroblastoma of the hands and feet. Design and patients: Twenty-five cases of pathologically proven chondroblastoma of the hands and feet were reviewed. Available imaging modalities included radiographs (n=24), CT (n=3), MRI (n=5), and radionuclide bone scintigraphy (n=1). The following imaging features for each case were tabulated: location, presence of sclerotic margin, calcification, expansion, presence of fluid/ fluid levels on cross-sectional imaging and surrounding edema on MRI. The images were evaluated for skeletal maturity using closure of the physeal plate in the region as a standard. Results: The average age at time of diagnosis was 23 years (range 7-57 years). Eighty-four percent (n=21) of the patients were skeletally mature. Males (20 of 25) outnumbered females by a ratio of 5:1. The bones of the foot accounted for 22 cases: calcaneus (n=8), talus (n=8), metatarsals (n=3), and the cuboid (n=3). The bones of the hand accounted for three cases: phalanx (n=1), triquetrum (n=1), and a metacarpal (n=1). Radiographically all lesions were osteolytic with identifiable calcification in 54% (13 of 24). Fluid/fluid levels were seen in four of five cases on MRI. Edema on MR images was seen in 40% (2 of 5). The size of the lesions ranged from 2 to 41 cm 2 . Conclusion: Chondroblastomas of the hands and feet share many of the radiographic characteristics seen in the long bones, but manifest in skeletally mature patients with a higher male to female ratio than in long bone chondroblastoma. Talar and calcaneal lesions were encountered only in males. Chondroblastoma of the wrist and hand appears to be exceptionally rare.

To identify associations between clinical symptoms of temporomandibular joint disorders and radiographic findings. Two hundred four adult patients (156 women, 48 men, mean age 40 years) with temporomandibular joint (TMJ) pain/sounds or changes in mandibular motion were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Bilateral sagittal corrected TMJ tomograms in closed and open positions were assessed for the presence of flattening, erosion, osteophytes, and sclerosis in the joint components and the range of mandibular motion. Logistic regression analyses were performed with the radiographic findings as the dependent variables and the following clinical variables as independent variables: opening pattern, maximal jaw opening, TMJ sounds, number of painful muscle/TMJ sites, duration of pain, presence of arthritic disease, depression and somatization scores, graded chronic pain, and age and gender. Coarse crepitus on opening/closing (odds ratio [OR] > or = 3.12), on lateral excursions (odds ratio > or = 4.06), and on protrusion (OR > or = 5.30) was associated with increased risk of degenerative findings in tomograms. A clinical diagnosis of osteoarthritis increased the risk of radiographic findings (OR > or = 2.95) and so did increasing age (OR > or = 1.03 per year) and the female gender (OR > or = 2.36). Maximal assisted opening and maximal opening without pain (< 40 mm) was associated with a posterior condyle-to-articular tubercle position (OR > or = 2.60). No other significant associations were observed. Age, gender, and coarse crepitus, but no pain-related variables, were associated with increased risk of degenerative findings in TMJ tomograms. Maximal opening < 40 mm was associated with a posterior condyle-to-articular tubercle relation on opening.

To identify associations between clinical symptoms of temporomandibular joint disorders and radiographic findings. Two hundred four adult patients (156 women, 48 men, mean age 40 years) with temporomandibular joint (TMJ) pain/sounds or changes in mandibular motion were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Bilateral sagittal corrected TMJ tomograms in closed and open positions were assessed for the presence of flattening, erosion, osteophytes, and sclerosis in the joint components and the range of mandibular motion. Logistic regression analyses were performed with the radiographic findings as the dependent variables and the following clinical variables as independent variables: opening pattern, maximal jaw opening, TMJ sounds, number of painful muscle/TMJ sites, duration of pain, presence of arthritic disease, depression and somatization scores, graded chronic pain, and age and gender. Coarse crepitus on opening/closing (od...

The aim of this report is to describe the management of a 16-year-old patient with oligodontia including six permanent teeth. Oligodontia is agenesis of six teeth or more, excluding third molars. The etiology of congenital absence of teeth is believed to be involved in heredity or developmental anomalies. It can be isolated or as part of a syndrome. There are a number of options available to restore space generated by missing teeth. Dental treatment can vary depending on the severity of the disease and generally requires a multidisciplinary approach. Treatment options include orthodontic therapy, implants, adhesive techniques, and removable prostheses. A 16-year-old male patient with oligodontia affecting six permanent teeth received conservative care that met his and his parent's expectations. The existing primary teeth were restored to resemble permanent teeth in order to achieve a favorable esthetic result using direct composite resin. The restorative treatment was provided f...

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate therapy, primarily diagnosed in patients with cancer and metastatic bone disease and receiving intravenous administrations of nitrogen-containing bisphosphonates. If diagnosis or treatment is delayed, BRONJ can develop to a severe and devastating disease. Numerous studies have focused on BRONJ, with possible pathomechanisms identified to be oversuppression of bone turnover, ischemia due to antiangiogenetic effects, local infections, or soft tissue toxicity. However, the precise pathogenesis largely remains elusive and questions of paramount importance await to be answered, namely 1) Why is only the jaw bone affected? 2) Why and how do the derivatives differ in their potency to induce a BRONJ? and 3) Why and when is BRONJ manifested? The present perspective reflects on existing theories and introduces the hypothesis that local tissue acidosis in the jaw bone offers a conclusive pathogenesis model and may prove to be the missing link in BRONJ.

The limitations of manual prosthesis crimping in hearing restoration surgery for otosclerosis are thought to have a key role in the occurrence of incomplete postoperative elimination of conductive hearing loss and postoperative recurrences of conductive hearing loss. To eliminate manual crimping, the self-crimping, shape-memory alloy Nitinol stapes piston was introduced in nine otosclerosis patients. The results were compared with those in a database of surgeries performed with conventional titanium pistons. The effects of the self-crimping Nitinol prosthesis on the postoperative elimination of conductive hearing loss and its postoperative variations were investigated. The variations of postoperative residual conductive hearing loss were significantly smaller and the extent of conductive hearing-loss elimination greater in the Nitinol group. The mean postoperative residual conductive hearing loss was smaller in the Nitinol group. The postoperative stability of conductive hearing loss elimination was similar in both patient groups. Preliminary results suggest that the selfcrimping shape-memory alloy Nitinol stapes piston overcomes the drawbacks of manual crimping in hearing restoration surgery for otosclerosis.

The detection of osteomas in the maxillofacial region may be the initial clinical finding in Gardner's syndrome (GS). The most common location of osteomas is in the skull, but the lesion can also occur in the jaws. We present a case of a 47 year old male patient with GS who was referred for radiological evaluation. Extraoral examination revealed an epidermoid cyst and the patient had a history of intestinal polyps. A panoramic radiograph demonstrated numerous osteomas and diffuse sclerosis of the mandible, and compound odontomas with impacted teeth. CT scan allowed the localization and extension of the osteomas, and showed other sites in the maxillofacial region as well. CT images also revealed a different behaviour of osteoma, invading the mandibular canal.

Granulomas hialinizantes são lesões fibrosantes benignas que em geral se apresentam radiologicamente sob a forma de nódulos múltiplos, freqüentemente escavados e/ou calcificados. Neste trabalho é relatado o caso de uma paciente de 28 anos de idade que apresentou a doença provavelmente secundária a infecção tuberculosa prévia. Ressalta-se a necessidade da inclusão deste diagnóstico diferencial frente ao quadro radiológico de múltiplas lesões nodulares. Unitermos: Granulomas hialinizantes; Nódulos pulmonares; Tomografia computadorizada.

Langerhans cell histiocytosis is a rare disease in childhood. It has a very polymorphous clinical expression, ranging from a single bony disease to a multisystemic disease involving vital organs. Prognosis has been improved by use of chemotherapy. We report a 2-year-old girl with multifocal Langerhans cell histiocytosis of bone and skin, revealed by a pain of the left hip and a limp trailing from 2 months. The diagnosis has been established by histological exam. The patient received chemotherapy and steroids. Outcome was favourable over 6-month follow-up. Trailing limp should evoke diagnosis of Langerhans cell histiocytosis. Skin biopsy should be preferred to a bone biopsy because of its safety.

We studied eight affected and four unaffected individuals from a Colombian family with autosomal dominant diffuse high bone density. Affected individuals have normal, proportional height and high serum alkaline phosphatase activity. Radiographically, affected members exhibit generalized, symmetrically diffuse endosteal hyperostosis of the long bones and skull with narrow medullary cavities and loss of the diploë , respectively. There is no periosteal reaction or decreased hematopoiesis. Furthermore, osteosclerosis affects vertebral bodies, ribs, pelvis, mandible, clavicles, and scapulae. Bone mineral density is 2.4 -7.3 SD above the mean for age and gender in affected individuals. Affected vs. unaffected individu-als' Z-scores were (mean ؎ SD) 5.03 ؎ 1.77 vs. 0.08 ؎ 0.97, respectively, P ‫؍‬ 0.0004). Three affected subjects older than 40 yr old lost bone mass in 6 yr. No dysmorphism, abnormal facial features, bone fractures, or cranial nerve involvement was found. The pattern of inheritance, the absence of asymmetries and malformations, the increased serum alkaline phosphatase, the peak bone mass that appears to decrease physiologically with age, and the involvement of cortical and trabecular bone suggest a new variant of hyperostosis/osteosclerosis that affects the entire skeleton. (J Clin Endocrinol Metab 88:

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused by mutations involving WTX (FAM123B), a tumor suppressor protein with dual functions. OSCS typically affects females whereas males generally have fetal or neonatal lethality. Surviving affected males have characteristic facial dysmorphisms, skeletal features such as macrocephaly and short stature, neurodevelopmental disabilities and a high prevalence of neuromuscular anomalies. On imaging, hemizygous males display marked cranial and peripheral skeletal sclerosis without the metaphyseal striations that are seen in women with OSCS. Observations of striation in males may be indicative of a somatic mosaic mutation in WTX. To date only two cases of surviving males haves been confirmed with mosaic point mutations in WTX. We report on the first case of a male with a mosaic deletion of the entire WTX gene. We show that a mosaic deletion in a hemizygous male patient can cause a mild phenotype of OSCS, including facial and skull base bone striations, nasal stenosis, conductive hearing loss, global developmental delay, and mild facial dysmorphology without short stature or macrocephaly.

We present the first successful report of mandibular reconstruction using a free fibula osteocutaneous flap in a patient with pyknodysostosis. The patient had recurrent refractory osteomyelitis of the mandible, which was initially treated with resection and reconstruction using an AO plate. Recurrent fistula formation with loosening of the plate was treated by radical re-excision and reconstruction with a free fibula flap. The postoperative course was uneventful; at 14 months the bony union was almost complete, without resorption or atrophy of the grafted fibula on radiography. 9 2001 The British Association of Plastic Surgeons SUMMARY. This case report describes a curious cause of insomnia. A 93-year-old woman presented to our follow-up clinic with the complaint of insomnia secondary to an audible click emanating from her scull. The site of loud biphasicsound production corresponded to an area of the scalp where a squamous cell carcinoma had been removed 11 years previously. 9 2001 The British Association of Plastic Surgeons

Introduction: Breast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice. Methods: The effects of 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α-and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels. Results: In vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH) 2 D 3 inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49 ± 0.08 mm 2 versus 1.68 ± 0.15 mm 2 , P b 0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81 ± 0.13 mm 2 versus 0.52 ± 0.11 mm 2 in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth. Conclusion: Vitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.

Ischial tuberosity pain in athletes may be caused by several clinical entities, which include acute and old bony or periosteal avulsions and apophysitis. We studied the natural course of these injuries based on our clinical case series of fourteen patients with apophysitis and twenty-one with avulsion of the ischial tuberosity. Only patients with the diagnosis confirmed by X-ray finding were included. The clinical diagnostic criteria by ischial apophysitis consisted of gradually increasing functional and palpatory pain at the ischial tuberosity without any major trauma at the beginning of the symptoms. Typically there was asymmetry on plain radiographs of the ischial tuberosities in apophysitis; the involved apophyseal area became sclerotic, wider than the non-symptomatic apophysis, osteoporotic patches developed and the lower margin of the ischial tuberosity became irregular. The patients with avulsion reported an acute trauma at the beginning of the symptoms and an avulsion fragment was immediately after injury or later seen in plain radiographs. The mean age of the patients with apophysitis (14.1 yrs) was lower than that of the subjects with avulsions (18.9 yrs). Apophysitis of the ischial tuberosity usually healed well without complications. Avulsions often caused more prolonged pain with referral pain to the posterior parts of the thigh which often required operative interventions. A small bony or periosteal avulsion sometimes grew to a pseudotumor calcification. We recommend conservative treatment as the primary treatment modality for both ischial tuberosity apophysitis and avulsion fractures.

We report a case of successful diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome based on monoclonality that was confirmed by an osteosclerotic lesion biopsy in a patient without pathognomonic symptoms or monoclonal gammopathy, probably because of comorbidities, which included systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome. A 57-year-old woman presented with an approximately 2-year history of numbness in the toes that had gradually spread, along with muscle weakness in both arms and legs. She had been receiving immunosuppressant and corticosteroid therapy since being diagnosed with systemic lupus erythematosus and Sjögren syndrome at the age of 31 years and rheumatoid arthritis at the age of 44 years. Neurological examination revealed predominantly distal hypoesthesia and weakness in a typical stocking-and-glove pattern. Immunoelectrophoresis revealed elevated polyclonal immunoglobulin, which...

Pycnodysostosis is a rare hereditary bone abnormality with an autosomal recessive mode of inheritance. We report the clinical, radiologic, and endocrine status of 8 children with this rare disease. All patients had the characteristic phenotype of the disorder including short stature (8 of 8), increased bone density (7 of 8), separated cranial sutures (8 of 8), large fontanel with delayed closure (8 of 8), obtuse mandibular angle (8 of 8), delayed teeth eruption (8 of 8), enamel hypoplasia (7 of 8), dysplastic acromial ends of the clavicles (6 of 8), frontal bossing (6 of 8), ocular proptosis (8 of 8), and dysplastic nails (8 of 8). Developmental evaluation according to the revised Denever developmental screening showed normal motor, fine motor-adaptive language, and personal social abilities in all the children. All had normal hepatic and renal functions. Serum calcium and phosphorus concentrations were normal. Two children had low serum alkaline phosphatase concentration. Short sta...

Newborn NMRI strain mice were infected with Reilly-Finkel-Biskis (RFB) murine leukemia virus (MuLV), a murine leukemia virus that has been shown to induce lymphomas , osteosclerosis , and osteomas in susceptible strains of mice. Bone histomorphometry of the distal femoral metaphyses at 3-month intervals showed osteosclerosis 3 (100%) , 6 (100%) , and 9 (93%) months after infection. This was represented by significantly augmented cancellous bone mass and accompanied by distinct changes in bone architecture. High numbers of provirus copies were detected at 2-4 weeks in femora , humeri , and calvaria, and viral protein was highly expressed in trabecular and cortical bone cells , particularly in osteocytes. Infected mice showed enhanced bone formation and smaller numbers of osteoclasts relative to sex-and agematched controls. Osteoclastic differentiation was significantly reduced in cocultures of spleen or bone marrow cells with RFB MuLV-infected osteoclastogenic , osteoblast-like cells. However , RFB MuLV did not impair the activity of mature osteoclasts. In infected mice lymphomas were only observed at 6 (22%) and 9 months (40%) of age. At 3 months, IgG gene and TCR-␤ gene rearrangements were not detectable , and new proviruses showed a heterogeneous integration pattern , indicating the absence of lymphoma in early osteosclerotic mice. In contrast, lymphomas , which developed in 8-to 9-month-old in-fected mice, showed IgG rearrangements indicating development of B-cell lymphomas, together with mono-or oligoclonal expansion of distinct patterns of proviral integrations. These results indicate that RFB MuLV-induced osteosclerosis develops within 3 months after infection and precedes lymphomagenesis. It may therefore be considered an independent skeletal lesion in MuLV-infected mice.

Evaluation of bone marrow fibrosis and osteosclerosis in myeloproliferative neoplasms (MPN) is subject to interobserver inconsistency. Performance data for currently utilized fibrosis grading systems are lacking, and classification scales for osteosclerosis do not exist. Digital imaging can serve as a quantification method for fibrosis and osteosclerosis. We used digital imaging techniques for trabecular area assessment and reticulin-fiber quantification. Patients with all Philadelphia negative MPN subtypes had higher trabecular volume than controls (p ≤0.0015). Results suggest that the degree of osteosclerosis helps differentiate primary myelofibrosis from other MPN. Numerical quantification of fibrosis highly correlated with subjective scores, and interobserver correlation was satisfactory. Digital imaging provides accurate quantification for osteosclerosis and fibrosis.

Osteolysis or osteosclerosis often occurs in bone tissue adjacent to chronic inflammatory processes. Numerous cytokines and inflammatory mediators have been implicated as osteoclast-activating agents, explaining inflammation-induced bone resorption. In many cases, the cause of the sclerosis seen in these lesions is less thoroughly investigated. We have studied the effects of thrombin and bradykinin, 2 inflammatory mediators, on the rate of proliferation in isolated human osteoblasts (hOBs).

A girl with fully expressed osteopathia striata with cranial sclerosis ( 0 s ) was also found to have a contraction of the two visual fields, a sign never previously described in 0s syndrome. We suggest that the visual field defect is a component manifestation of 0s syndrome, whose pathogenesis is represented by distortion of the optic canal and narrowing of the optic foramina.

Dysosteosclerosis is a rare autosomal recessive skeletal dysplasia characterized by osteosclerosis and platyspondyly. A case of dysosteosclerosis in a 17-year-old male from our institution was first published by Houston et al. [1978]. This patient has survived into adulthood and to our knowledge, is the only reported adult with dysosteosclerosis. We will review the clinical and radiographic features in our patient.

Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to -2.3 SD. Head circumference was þ4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology. ß

Although articular cartilage is the primary tissues affected by osteoarthritis (OA), the underlying subchondral bone also undergoes noticeable changes. Despite the growing body of research into the biophysical and mechanical properties of OA bone there are few studies that have analysed the structure of the subchondral sclerosis at the nanoscale. In this study, the composition and nano-structural changes of human osteoarthritis (OA) subchondral bone were investigated to better understand the site-specific changes. OA bone samples were collected from patients undergoing total knee replacement surgery and graded according to disease severity (grade I: mild OA; grade IV: severe OA). Transmission electron microscopy (TEM), Electron Diffraction, and Elemental Analysis techniques were used to explore the cross-banding pattern, nature of mineral phase and orientation of the crystal lattice. Subchondral bone nano-hydroxyapatite powders were prepared and characterised using high resolution t...