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Genes & Development Dec 1999
Review
Topics: Animals; Bone Development; Bone Remodeling; Bone and Bones; Calcification, Physiologic; Calcitonin; Calcitriol; Cell Differentiation; Cytokines; Extracellular Matrix; Growth Substances; Hedgehog Proteins; Humans; Mammals; Mice; Mice, Mutant Strains; Models, Biological; Neoplasm Proteins; Osteoblasts; Osteoclasts; Osteogenesis; Osteopetrosis; Osteoporosis; Osteosclerosis; Parathyroid Hormone; Proteins; Trans-Activators; Transcription Factors; Transcription, Genetic
PubMed: 10601030
DOI: 10.1101/gad.13.23.3037 -
BMJ Case Reports May 2015
Topics: Adult; Humans; Knee; Low Back Pain; Male; Osteopoikilosis; Pelvis; Physical Therapy Modalities; Physical Therapy Specialty; Tomography, X-Ray Computed
PubMed: 25939972
DOI: 10.1136/bcr-2014-208422 -
European Archives of Paediatric... Aug 2021Dense Bone Islands (DBIs) are anatomic variants defined as radiopaque lesions consisting of hamartomatous cortical bone, often presenting as incidental radiographic...
BACKGROUND
Dense Bone Islands (DBIs) are anatomic variants defined as radiopaque lesions consisting of hamartomatous cortical bone, often presenting as incidental radiographic findings. DBIs can also be known as idiopathic osteosclerosis, bone whorl, focal periapical osteopetrosis, bone scar and enostosis. We found a paucity of literature for management and reporting of this condition in children. For this reason, the authors describe sixteen cases of children and adolescents with dense bony islands and suggest a pathway for management.
CASE SERIES
Cases presented to the RNENT and Eastman Dental Hospital or private practice, either as chance findings or for diagnosis and treatment planning of undiagnosed radiopaque areas. The individuals were aged between 10 and 17 years; 6 boys and 10 girls. All radiographic reports described DBIs. Diagnoses were confirmed by a Dental and Maxillofacial Radiology Consultant and advised no intervention. In some cases, monitoring was advised. Caution in orthodontic tooth movement was advised for five patients.
CONCLUSION
DBIs are common findings that seldom require treatment; however, caution should be exercised when undertaking orthodontic movement in the area of a DBI due to a potential risk of root resorption. Accurate identification and multidisciplinary management are of utmost importance.
Topics: Adolescent; Child; Female; Humans; Islands; Male; Osteopetrosis; Osteosclerosis; Radiography; Root Resorption
PubMed: 33423206
DOI: 10.1007/s40368-020-00596-w -
Bone Jul 2022The cellular and molecular mechanisms of bone development and homeostasis are clinically important, but not fully understood. Mutations in integrins and Kindlin3 in...
The cellular and molecular mechanisms of bone development and homeostasis are clinically important, but not fully understood. Mutations in integrins and Kindlin3 in humans known as Leukocyte adhesion deficiencies (LAD) cause a wide spectrum of complications, including osteopetrosis. Yet, the rarity, frequent misdiagnosis, and lethality of LAD preclude mechanistic analysis of skeletal abnormalities in these patients. Here, using inducible and constitutive tissue-specific Kindlin3 knockout (K3KO) mice, we show that the constitutive lack of embryonic-Kindlin3 in myeloid lineage cells causes growth retardation, edentulism, and skull deformity indicative of hydrocephaly. Micro-CT analysis revealed craniosynostosis, choanal stenosis, and micrognathia along with other skeletal abnormalities characteristic of osteopetrosis. A marked progression of osteosclerosis occurs in mature to middle-aged adults, resulting in the narrowing of cranial nerve foramina and bone marrow cavities of long bones. However, postnatal-Kindlin3 is less critical for bone remodeling and architecture. Thus, myeloid Kindlin3 is essential for skeletal development and its deficiency leads to autosomal recessive osteopetrosis (ARO). The study will aid in the diagnosis, management, and treatment choices for patients with LAD-III and ARO.
Topics: Animals; Bone Remodeling; Bone and Bones; Humans; Mice; Middle Aged; Mutation; Osteopetrosis
PubMed: 35342016
DOI: 10.1016/j.bone.2022.116397 -
International Journal of Paleopathology Jun 2021A reappraisal of the available evidence of osteopetrosis in the archaeological record as first step in promoting new approaches to rare diseases in paleopathology. (Review)
Review
OBJECTIVE
A reappraisal of the available evidence of osteopetrosis in the archaeological record as first step in promoting new approaches to rare diseases in paleopathology.
MATERIALS AND METHODS
Three different approaches are combined: a survey of the last 50 years of bioarchaeological publications; an online search addressing six of the more widely used search engines; macroscopic and radiographic analyses of the human remains from the Neolithic site of Palata 2 (Italy).
RESULTS
The combined results of the literature survey and the online search identified six cases of osteopetrosis. The majority of search hits place this disease into differential diagnoses. The investigation of the remains from Palata 2, one of the six cases in literature, indicates a non-specific sclerosis of the cranial vault.
CONCLUSIONS
Of the six cases of osteopetrosis, only two, one of the autosomal-recessive type (ARO) and one of the autosomal-dominant type (ADO), are supported by direct osteoarchaeological evidence. Therefore, inaccurate differential diagnoses generate an inflated number of cases in the paleopathological record.
SIGNIFICANCE
This reappraisal calls for a more informed and evidence-based approach to osteopetrosis and, more generally, to rare diseases in paleopathology.
LIMITATIONS
Lack of specific publications on osteopetrosis; more case studies may be present in "gray literature".
SUGGESTIONS FOR FURTHER RESEARCH
Cases of osteopetrosis from archaeological and historical collections as well as medical literature are needed to increase knowledge about this rare disease. More precise differential diagnoses are required, particularly when dealing with rare diseases.
Topics: Anthropology; Diagnosis, Differential; Humans; Osteopetrosis; Paleopathology; Rare Diseases
PubMed: 34082191
DOI: 10.1016/j.ijpp.2021.05.006 -
Indian Journal of Dental Research :... 2010Osteopetrosis is a descriptive term that refers to a group of rare, heritable disorders of the skeleton. Osteopetrotic conditions vary greatly in their presentation and... (Review)
Review
Osteopetrosis is a descriptive term that refers to a group of rare, heritable disorders of the skeleton. Osteopetrotic conditions vary greatly in their presentation and severity, from just as an incidental finding on radiographs to causing life-threatening complications such as bone marrow suppression. It is caused by failure of osteoclast development and function. Osteopetrosis can be inherited as autosomal-recessive, autosomal-dominant or as X-linked traits, with the most severe forms being the autosomal-recessive ones. The severity of the disease is mild to moderate in the autosomal-dominant forms, with normal life expectancy. Diagnosis is largely based on clinical and radiographic evaluation. The present paper reports a case of autosomal-dominant osteopetrosis complicated by osteomyelitis with a short review of the condition.
Topics: Adult; Chronic Disease; Diagnosis, Differential; Genes, Dominant; Humans; Incidental Findings; Male; Mandibular Diseases; Osteomyelitis; Osteopetrosis; Osteosclerosis; Radiography, Panoramic; Suppuration
PubMed: 21187637
DOI: 10.4103/0970-9290.74234 -
Bone Apr 2021Skeletal fluorosis (SF) is endemic primarily in regions with fluoride (F)-contaminated well water, but can reflect other types of chronic F exposure. Calcium (Ca) and... (Review)
Review
Skeletal fluorosis (SF) is endemic primarily in regions with fluoride (F)-contaminated well water, but can reflect other types of chronic F exposure. Calcium (Ca) and vitamin D (D) deficiency can exacerbate SF. A 51-year-old man with years of musculoskeletal pain and opiate use was hypocalcemic with secondary hyperparathyroidism upon manifesting recurrent long bone fractures. He smoked cigarettes, drank large amounts of cola beverage, and consumed little dietary Ca. Then, after 5 months of Ca and D supplementation, serum 25(OH)D was 21 ng/mL (Nl, 30-100), corrected serum Ca had normalized from 7.8 to 9.4 mg/dL (Nl, 8.5-10.1), alkaline phosphatase (ALP) had decreased from 1080 to 539 U/L (Nl, 46-116), yet parathyroid hormone (PTH) had increased from 133 to 327 pg/mL (Nl, 8.7-77.1). Radiographs revealed generalized osteosclerosis and a cystic lesion in a proximal femur. DXA BMD Z-scores were +7.4 and +0.4 at the lumbar spine and "1/3" radius, respectively. Bone scintigraphy showed increased uptake in two ribs, periarticular areas, and proximal left femur at the site of a subsequent atraumatic fracture. Elevated serum collagen type I C-telopeptide 2513 pg/mL (Nl, 87-345) and osteocalcin >300 ng/mL (Nl, 9-38) indicated rapid bone turnover. Negative studies included hepatitis C Ab, prostate-specific antigen, serum and urine electrophoresis, and Ion Torrent mutation analysis for dense or high-turnover skeletal diseases. After discovering markedly elevated F concentrations in his plasma [4.84 mg/L (Nl, 0.02-0.08)] and spot urine [42.6 mg/L (Nl, 0.2-3.2)], a two-year history emerged of "huffing" computer cleaner containing difluoroethane. Non-decalcified histology of a subsequent right femur fracture showed increased osteoblasts and osteoclasts and excessive osteoid. A 24-hour urine collection contained 27 mg/L F (Nl, 0.2-3.2) and <2 mg/dL Ca. Then, 19 months after "huffing" cessation and improved Ca and D intake, yet with persisting bone pain, serum PTH was normal (52 pg/mL) and serum ALP and urine F had decreased to 248 U/L and 3.3 mg/L, respectively. Our experience combined with 15 publications in PubMed concerning unusual causes of non-endemic SF where the F source became known (19 cases in all) revealed: 11 instances from high consumption of black tea and/or F-containing toothpaste, 1 due to geophagia of F-rich soil, and 7 due to "recreational" inhalation of F-containing vapors. Circulating PTH measured in 14 was substantially elevated in 2 (including ours) and mildly increased in 2. The severity of SF in the cases reviewed seemed to reflect cumulative F exposure, renal function, and Ca and D status. Several factors appeared to influence our patient's skeletal disease: i) direct anabolic effects of toxic amounts of F on his skeleton, ii) secondary hyperparathyroidism from degradation-resistant fluorapatite bone crystals and low dietary Ca, and iii) impaired mineralization of excessive osteoid due to hypocalcemia.
Topics: Bone Density; Bone Diseases; Humans; Hyperparathyroidism, Secondary; Male; Middle Aged; Osteosclerosis; Parathyroid Hormone; Spine
PubMed: 33418099
DOI: 10.1016/j.bone.2021.115839 -
Journal of the Royal Society of Medicine Apr 2005
Topics: Aged; Erdheim-Chester Disease; Humans; Hydronephrosis; Male; Osteosclerosis; Radionuclide Imaging
PubMed: 15805559
DOI: 10.1177/014107680509800408 -
FASEB Journal : Official Publication of... Sep 2022Autosomal dominant osteopetrosis type II (ADO2) is a heritable bone disease of impaired osteoclastic bone resorption caused by missense mutations in the chloride channel...
Autosomal dominant osteopetrosis type II (ADO2) is a heritable bone disease of impaired osteoclastic bone resorption caused by missense mutations in the chloride channel 7 (CLCN7) gene. Clinical features of ADO2 include fractures, osteomyelitis of jaw, vision loss, and in severe cases, bone marrow failure. Currently, there is no effective therapy for ADO2, and patients usually receive symptomatic treatments. Theoretically, bone marrow transplantation (BMT), which is commonly used in recessive osteopetrosis, could be used to treat ADO2, although the frequency of complications related to BMT is quite high. We created an ADO2 knock-in (p.G213R mutation) mouse model on the 129 genetic background, and their phenotypes mimic the human disease of ADO2. To test whether BMT could restore osteoclast function and rescue the bone phenotypes in ADO2 mice, we transplanted bone marrow cells from 6-8 weeks old male WT donor mice into recipient female ADO2 mice. Also, to determine whether age at the time of transplant may play a role in transplant success, we performed BMT in young (12-week-old) and old (9-month-old) ADO2 mice. Our data indicate that ADO2 mice transplanted with WT marrow achieved more than 90% engraftment up to 6 months post-transplantation at both young and old ages. The in-vivo DXA data revealed that young ADO2 mice transplanted with WT marrow had significantly lower whole body and spine areal bone mineral density (aBMD) at month 6 post-transplantation compared to the ADO2 control mice. The old ADO2 mice also displayed significantly lower whole body, femur, and spine aBMD at months 4 and 5 post-transplantation compared to the age-matched control mice. The in-vivo micro-CT data showed that ADO2 experimental mice transplanted with WT marrow had significantly lower BV/TV at months 2 and 4 post-transplantation compared to the ADO2 control mice at a young age. In contrast, ADO2 control and experimental mice displayed similar BV/TV values for all post-transplantation time points at old age. In addition, serum CTX was significantly higher at month 2 post-transplantation in both young and old ADO2 experimental mice compared to the ADO2 control mice. Serum P1NP levels in young ADO2 experimental mice were significantly higher at baseline and month 2 post-transplantation compared to the ADO2 control mice. These data suggest that BMT may provide, at least, some beneficial effect at both young and adult ages.
Topics: Animals; Biomarkers; Bone Marrow Transplantation; Bone Resorption; Chloride Channels; Female; Humans; Infant; Male; Mice; Osteoclasts; Osteopetrosis
PubMed: 35959867
DOI: 10.1096/fj.202200678R -
PM & R : the Journal of Injury,... May 2023Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history... (Observational Study)
Observational Study
INTRODUCTION
Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history study, four outcome measures were administered to better understand the burden this disease has on a person's ability to engage in basic and instrumental activities of daily living.
OBJECTIVE
To investigate the relationship between functional engagement, fatigue, and motor ability in patients with melorheostosis.
DESIGN
Cross-sectional data gathered from a longitudinal natural history observational study.
SETTING
Rehabilitation department within a single institution.
PARTICIPANTS
Forty-seven adult volunteers with melorheostosis were enrolled. Two participants were removed for failure to meet diagnosis eligibility. Thirty patients had lower extremity (LE) osteosclerotic bone lesions, 14 had upper extremity (UE) lesions, and one had lesions in both UEs and LEs.
INTERVENTIONS
Not applicable.
MAIN OUTCOME MEASURES
Activity Card Sort, Second Edition (ACS); Multi-Dimensional Fatigue Inventory; Lower Extremity Functional Scale; Upper Extremity Functional Index.
RESULTS
On the ACS, high-demand leisure (HDL) activities were the least retained (p < .001). Of the activities rated most important, HDL activities were the most likely to have been given up (27%). General fatigue (μ = 11.8) and physical fatigue (μ = 11.0) were the two most limiting fatigue constructs. There were moderate negative correlations with HDL activities compared to physical fatigue (r = -0.524, p < .001) and reduced activity fatigue (r = -0.58, p = .001). LE lesions had a large effect on completing LE tasks (d = 0.95) and UE lesions had a medium effect on completing tasks involving the UE (d = 0.69).
CONCLUSIONS
Patients with melorheostosis experience fatigue and low engagement in HDL activities. The results of this study underscore the importance of acknowledging activity domain, fatigue constructs, and lesion location to support and provide targeted evidence-based rehabilitative therapy.
CLINICAL TRIAL REGISTRATION NUMBER
NCT02504879.
Topics: Adult; Humans; Activities of Daily Living; Cross-Sectional Studies; Fatigue; Lower Extremity; Melorheostosis; Upper Extremity
PubMed: 35403375
DOI: 10.1002/pmrj.12817