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Acta Reumatologica Portuguesa 2009
Topics: Adult; Humans; Male; Osteopetrosis; Radiography
PubMed: 19365311
DOI: No ID Found -
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 -
The Indian Journal of Medical Research Jan 2022
Topics: Humans; Osteomyelitis; Osteopetrosis
PubMed: 35859433
DOI: 10.4103/ijmr.IJMR_2340_20 -
Frontiers in Endocrinology 2020Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical... (Review)
Review
Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the drug development process and a molecular redefinition of skeletal disease can help overcoming current shortcomings in pharmaceutical research, including failed attempts and appalling costs. This review summarizes the achievements of genetic studies in the bone field and their application to clinical care, illustrating the imminent advent of the genomic medicine era.
Topics: Bone Diseases, Developmental; Drug Discovery; Gene Editing; Humans; Hyperostosis; Mendelian Randomization Analysis; Osteochondrodysplasias; Osteogenesis Imperfecta; Osteopetrosis; Osteoporosis; Syndactyly
PubMed: 33162933
DOI: 10.3389/fendo.2020.556610 -
Orphanet Journal of Rare Diseases Dec 2019Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment... (Review)
Review
BACKGROUND
Rare bone diseases account for 5% of all birth defects yet very few have personalised treatments. Developments in genetic diagnosis, molecular techniques and treatment technologies however, are leading to unparalleled therapeutic advance. This review explores the evolving therapeutic landscape of genetic skeletal disorders (GSDs); the key conditions and there key differentials.
METHODS
A retrospective literature based review was conducted in December 2018 using a systematic search strategy for relevant articles and trials in Pubmed and clinicaltrials.gov respectively. Over 140 articles and 80 trials were generated for review.
RESULTS
Over 20 personalised therapies are discussed in addition to several novel disease modifying treatments in over 25 GSDs. Treatments discussed are at different stages from preclinical studies to clinical trials and approved drugs, including; Burosumab for X-linked hypophosphatemia, Palovarotene for Hereditary Multiple Exostoses, Carbamazepine for Metaphyseal Chondrodysplasia (Schmid type), Lithium carbonate and anti-sclerostin therapy for Osteoporosis Pseudoglioma syndrome and novel therapies for Osteopetrosis. We also discuss therapeutic advances in Achondroplasia, Osteogenesis Imperfecta (OI), Hypophosphotasia (HPP), Fibrodysplasia Ossificans Progressiva, and RNA silencing therapies in preclinical studies for OI and HPP.
DISCUSSION
It is an exciting time for GSD therapies despite the challenges of drug development in rare diseases. In discussing emerging therapies, we explore novel approaches to drug development from drug repurposing to in-utero stem cell transplants. We highlight the improved understanding of bone pathophysiology, genetic pathways and challenges of developing gene therapies for GSDs.
Topics: Animals; Bone Diseases; Female; Humans; Male; Myositis Ossificans; Osteogenesis Imperfecta; Osteopetrosis; Rare Diseases
PubMed: 31888683
DOI: 10.1186/s13023-019-1222-2 -
Journal of Medical Genetics Mar 1988
Topics: Bone Diseases, Developmental; Cranial Nerve Diseases; Diagnosis, Differential; Female; Genes, Recessive; Gigantism; Humans; Intracranial Pressure; Male; Nerve Compression Syndromes; Osteopetrosis; Osteosclerosis; Syndrome
PubMed: 3351908
DOI: 10.1136/jmg.25.3.200 -
Proceedings of the Royal Society of... Aug 1972
Topics: Calcium, Dietary; Child; Diet Therapy; Humans; Infant; Male; Osteopetrosis
PubMed: 5085970
DOI: No ID Found -
Skeletal Radiology May 2021To characterize relationships between quantitative computed tomography bone mineral density measurements and other qualitative and quantitative imaging measures, as well...
OBJECTIVE
To characterize relationships between quantitative computed tomography bone mineral density measurements and other qualitative and quantitative imaging measures, as well as clinical metrics, in patients with autosomal dominant osteopetrosis type 2 (ADO2).
MATERIALS AND METHODS
Clinical and radiologic parameters of 9 adults and 3 children with autosomal dominant osteopetrosis type 2 were assessed including lumbar spine quantitative computed tomography (QCT), radiographic skeletal survey (skull base thickening; Erlenmeyer flask deformity; endobone pattern; and spine density pattern (endplate sclerosis, "anvil" appearance, or diffuse sclerosis)), dual-energy x-ray absorptiometry (DXA), tibial peripheral quantitative computed tomography (pQCT) volumetric bone mineral density (vBMD), bone turnover markers, and bone marrow failure or visual impairment.
RESULTS
The skeletal parameter most divergent from normal was lumbar spine QCT Z-score (+ 3.6 to + 38.7). Lumbar QCT Z-score correlated positively with pQCT tibial diaphysis vBMD (Pearson correlation r = 0.73, p = 0.02) and pQCT tibial metaphysis vBMD (r = 0.87, p < 0.01). A trend towards positive lumbar QCT Z-score correlation with serum P1NP/CTX ratio (r = 0.54, p = 0.10) and lumbar DXA Z-score (r = 0.55, p = 0.10) were observed. Bone marrow failure and vision impairment occurred in those with most severe quantitative and qualitative measures, while those with less severe radiographic features had the lowest QCT Z-scores.
CONCLUSION
Lumbar spine QCT provided the most extreme skeletal assessment in ADO2, which correlated positively with other radiologic and clinical markers of disease severity. Given the quantification of trabecular bone and greater variation from normal with wider range of values, lumbar QCT Z-scores may be useful to determine or detect impact of future treatments.
Topics: Absorptiometry, Photon; Adult; Bone Density; Bone and Bones; Child; Humans; Lumbar Vertebrae; Osteopetrosis; Severity of Illness Index
PubMed: 33009917
DOI: 10.1007/s00256-020-03625-3 -
Journal of Molecular Medicine (Berlin,... Apr 2024Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and... (Review)
Review
Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.
Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and undercarboxylated OC (ucOC). While cOC promotes bone mineralization and increases bone strength, ucOC is regarded an endocrinologically active form that may have several functions in multiple end organs and tissues. Total OC (tOC) includes both of these forms (cOC and ucOC) and is considered a marker of bone turnover in clinical settings. Most of the data on OC is limited to preclinical studies and therefore may not accurately reflect the situation in clinical conditions. For the stated reason, the aim of this review was not only to summarize current knowledge of all forms of OC and characterize its role in diabetes mellitus, osteoporosis, osteopetrosis, inflammatory joint diseases, but also to provide new interpretations of its involvement in the management and treatment of aforementioned diseases. In this context, special emphasis was placed on available clinical trials. Significantly lower levels of tOC and ucOC could be associated with the risk of type 2 diabetes mellitus. On the contrary, tOC level does not seem to be a good indicator of high bone turnover status in postmenopausal osteoporosis, osteoarthritis and rheumatoid arthritis. The associations between several pharmacological drugs used to treat all disorders mentioned above and OC levels have also been provided. From this perspective, OC may serve as a medium through which certain medications can influence glucose metabolism, body weight, adiponectin secretion, and synovial inflammation.
Topics: Humans; Diabetes Mellitus, Type 2; Osteocalcin; Osteopetrosis; Osteoporosis; Joint Diseases; Biomarkers
PubMed: 38363329
DOI: 10.1007/s00109-024-02418-8 -
The Cornell Veterinarian Apr 1981Yearling heifers overfed protein, calcium and phosphorus with a feed recommended for high producing dairy cows developed osteopetrosis and skeletal malformations as a...
Yearling heifers overfed protein, calcium and phosphorus with a feed recommended for high producing dairy cows developed osteopetrosis and skeletal malformations as a result of retarded bone resorption. Histologic and electron microscopic examinations showed that C cell hyperplasia was also present. The presence of C cell hyperplasia and osteopetrosis supported the diagnosis of hypercalcitoninism. Clinically unaffected heifers were studied by serum chemistry after 1 to 1.5 months on the same diet at age 6 months and after 3 months on an optimal diet to learn whether they showed evidence of hypercalcitoninism as expressed by retarded bone resorption and/or hypercalcitoninemia. The data indicated that bone resorption was retarded and that serum gastrin was elevated in the heifers without skeletal malformations while on the high calcium feed. The heifers were isocalcitoninemic. The data suggested that overfeeding calcium was sufficient to produce hypercalcitoninism but the rate of calcitonin secretion had not exceeded the rate of removal of calcitonin from blood by binding to tissue receptors and by metabolic degradation. Since calcitonin is rapidly removed from blood, hypercalcitoninism may occur without concomitant hypercalcitoninemia.
Topics: Animal Feed; Animal Husbandry; Animals; Calcitonin; Calcium, Dietary; Cartilage, Articular; Cattle; Cattle Diseases; Female; Osteopetrosis; Radiography
PubMed: 7214919
DOI: No ID Found