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Osteopetrosis Differential Diagnoses

  • Author: Robert Blank, MD, PhD; Chief Editor: George T Griffing, MD  more...
 
Updated: Dec 17, 2014
 
 

Diagnostic Considerations

In the differential diagnosis, include conditions that can result in diffuse osteosclerosis. Such disorders may include congenital diseases (eg, pyknodysostosis,[16] hypoparathyroidism, pseudohypoparathyroidism), chemical poisoning (eg, fluoride, lead, beryllium), malignancies (leukemia, myeloproliferative diseases), and sickle cell disease. Osteoblastic metastases should also be considered in the differential diagnosis.

Differential Diagnoses

 
 
Contributor Information and Disclosures
Author

Robert Blank, MD, PhD Professor of Medicine, Cell Biology, and Physiology, Chief, Division of Endocrinology, Metabolism, and Clinical Nutrition, Director, TOPS Obesity Center, Medical College of Wisconsin; Staff Physician, Clement J Zablocki Veterans Affairs Medical Center

Robert Blank, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Society of Human Genetics, Central Society for Clinical and Translational Research, International Bone and Mineral Society, International Society for Clinical Densitometry, American College of Physicians, American Society for Bone and Mineral Research, Endocrine Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bristol-Myers Squibb.

Coauthor(s)

Anuj Bhargava, MD, MBA Adjunct Assistant Professor, Drake College of Pharmacy; Co-Director, Diabetes Institute, Mercy Medical Center; President, Iowa Diabetes and Endocrinology Research Center; President, My Diabetes Home, LLC

Anuj Bhargava, MD, MBA is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association

Disclosure: Received honoraria from Merck for speaking, research trials; Received honoraria from Novo Nordisk for speaking and teaching; Received honoraria from Sanofi for speaking and teaching; Received honoraria from takeda for speaking and teaching; Received honoraria from Abbott for speaking and teaching; Received grant/research funds from Lilly for research trials; Received grant/research funds from Gilead for research trials; Received grant/research funds from Novartis for research trials; Received gr.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Romesh Khardori, MD, PhD, FACP Former Professor, Department of Medicine, Former Chief, Division of Endocrinology, Metabolism, and Molecular Medicine, Southern Illinois University School of Medicine

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Stanley Wallach, MD Executive Director, American College of Nutrition; Clinical Professor, Department of Medicine, New York University School of Medicine

Stanley Wallach, MD is a member of the following medical societies: American College of Nutrition, American Society for Bone and Mineral Research, American Society for Clinical Investigation, American Society for Clinical Nutrition, American Society for Nutritional Sciences, Association of American Physicians, and Endocrine Society

Disclosure: Nothing to disclose.

References
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Table 1. Clinical Classification of Human Osteopetrosis
CharacteristicAdult onsetInfantileIntermediate
InheritanceAutosomal dominant[3] Autosomal recessiveAutosomal recessive
Bone marrow failureNoneSevereNone
PrognosisGoodPoorPoor
DiagnosisOften diagnosed incidentallyUsually diagnosed before age 1yNot applicable
Table 2. Molecular Lesions Leading to Osteopetrosis in the Mouse
GeneProteinLesionPhenotypeHuman EquivalentKey References
Csf1M-CSFNaturally occurring op allele (frame shift)Reduced size, short limbs, domed skull, absence of teeth, poor hearing, poor fertility, extramedullary hematopoiesis, rescued by administration of M-CSF None knownYoshida et al, 1990
Csf1rM-CSF receptorTargeted disruption in exon 3Reduced size, short limbs, domed skull, absence of teeth, poor fertility, extramedullary hematopoiesis, slightly more severe than Csf1opphenotype None knownDai et al, 2002
Tnfsf11RANKLTargeted disruptionsOsteopetrosis, failure of lymph nodes to developNone knownKong et al, 1999; Kim et al, 2000
Tnfrsf11aRANKTargeted disruptionsOsteopetrosis, failure of lymph nodes to developDuplications in exon 1 found in Paget disease and in familial expansile osteolysisLi et al, 2000
Ostm1Osteopetrosis-associated transmembrane protein 1Naturally occurring deletionAbnormal coat color, short lifespan, chondrodysplasia, failure of tooth eruption, osteopetrosisInfantile malignant osteopetrosisChalhoub et al, 2003
Acp5Tartrate resistant acid phosphatase (acid phosphatase 5)Targeted disruptionChondrodysplasia, osteopetrosisNone knownHayman et al, 1996
Car2Carbonic anhydrase IIN -ethyl-N -nitrosourea (ENU) mutagenesisNo skeletal phenotype in mouse, renal tubular acidosis, growth retardationOsteopetrosis with renal tubular acidosisLewis et al, 1988
Clcn7Chloride channel 7Targeted disruptionsChondrodysplasia, osteopetrosis, failure of tooth eruption, optic atrophy, retinal degeneration, premature deathAutosomal dominant type 2 osteopetrosis, autosomal recessive osteopetrosisKornak et al, 2001; Cleiren et al, 2001
CtskCathepsin KTargeted disruptionOsteopetrosis with increased osteoclast surfacePycnodysostosisSaftig et al, 1998; Kiviranta et al, 2005
Gab2Grb2 -associated binder 2Targeted disruptionOsteopetrosis, defective osteoclast maturationNone knownWada et al, 2005
MitfMicro-ophthalmia–associated transcription factorSpontaneous mutations, ENU mutagenesis, radiation mutagenesis, targeted disruption, untargeted insertional mutagenesisPigmentation failure, failure of tooth eruption, osteopetrosis, microphthalmia, infertility in both sexesWaardenburg syndrome, type 2a; Tietz syndrome, ocular albinism with sensorineural deafnessHodgkinson et al, 1993; Steingrimsson et al, 1994
Srcc-SRCTargeted disruptionOsteopetrosis, failure of tooth eruption, premature death, reduced body size, female infertility, poor nursingNone knownSoriano et al, 1991
Tcirg1116-kD subunit of vacuolar proton pumpSpontaneous deletion, targeted disruptionOsteopetrosis, failure of tooth eruption, chondrodysplasia, small size, premature deathAutosomal recessive osteopetrosisLi et al, 1999; Scimeca et al, 2000; Frattini et al, 2000
Traf6Tumor necrosis factor (TNF)-receptor–associated factor 6Targeted disruptionsOsteopetrosis, failure of tooth eruption, decreased body size, premature death, impaired maturation of dendritic cellsNone knownNaito et al, 1999; Lomaga et al, 1999; Kobayashi et al, 2003
Table 3. Types of Adult Osteopetrosis
CharacteristicType IType II
Skull sclerosisMarked sclerosis mainly of the vaultSclerosis mainly of the base
SpineDoes not show much sclerosisShows the rugger-jersey appearance
PelvisNo endobonesShows endobones in the pelvis
Transverse banding of metaphysisAbsentMay or may not be present
Risk of fractureLowHigh
Serum acid phosphataseNormalVery high
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