Indian Journal of Nuclear Medicine
Home | About IJNM | Search | Current Issue | Past Issues | Instructions | Ahead of Print | Online submissionLogin 
Indian Journal of Nuclear Medicine
  Editorial Board | Subscribe | Advertise | Contact
Users Online: 155 Print this page  Email this page Small font size Default font size Increase font size

 Table of Contents     
Year : 2015  |  Volume : 30  |  Issue : 1  |  Page : 55-58  

Osteopetrosis: Radiological & Radionuclide Imaging

1 School of Medicine, King's College London, United Kingdom
2 Department of Nuclear Medicine, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom

Date of Web Publication23-Dec-2014

Correspondence Address:
Cherry Sit
School of Medicine, King's College London, London
United Kingdom
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-3919.147544

Rights and Permissions

Osteopetrosis is a rare inherited bone disease where bones harden and become abnormally dense. While the diagnosis is clinical, it also greatly relies on appearance of the skeleton radiographically. X-ray, radionuclide bone scintigraphy and magnetic resonance imaging have been reported to identify characteristics of osteopetrosis. We present an interesting case of a 59-year-old man with a history of bilateral hip fractures. He underwent 99m Tc-methylene diphosphonate whole body scan supplemented with single-photon emission computed tomography/computed tomography of spine, which showed increased uptake in the humeri, tibiae and femora, which were in keeping with osteopetrosis.

Keywords: Dual-energy X-ray absorptiometry, osteopetrosis, single-photon emission computed tomography/computed tomography

How to cite this article:
Sit C, Agrawal K, Fogelman I, Gnanasegaran G. Osteopetrosis: Radiological & Radionuclide Imaging. Indian J Nucl Med 2015;30:55-8

How to cite this URL:
Sit C, Agrawal K, Fogelman I, Gnanasegaran G. Osteopetrosis: Radiological & Radionuclide Imaging. Indian J Nucl Med [serial online] 2015 [cited 2022 May 21];30:55-8. Available from:

   Introduction Top

Osteopetrosis, translated as "stone bone," is a rare inherited bone disease. It is also known as marble bone disease where bones harden and become abnormally dense, opposite to osteoporosis where bones become less dense and more brittle, or osteomalacia where bones soften. Various modalities of imaging have been shown to be useful in detecting and diagnosing osteopetrosis.

   Case Report Top

A 59-year-old man with the previous history of bilateral hip fractures was referred for a bone scan to rule out osteopetrosis and assess site of increased metabolic activity. Dual-energy X-ray absorptiometry (DXA) scan revealed high bone density [Figure 1]b and c. Patient underwent 99m Tc-methylene diphosphonate (MDP) whole body scan supplemented with single-photon emission computed tomography (SPECT)/computed tomography (CT) of the spine. 99m Tc-MDP bone scan showed increased tracer uptake at the proximal ends of humeri and tibiae, proximal and distal ends of femora [Figure 2]a. Linear uptake in the proximal femora and several lower ribs bilaterally was also noted and suggestive of fractures. SPECT images of the spine were unremarkable [Figure 2]b. CT scan showed dense sclerosis at the margins of the vertebral bodies (bone-in-bone appearance) and within the pelvic bones [Figure 1]d and e. The overall bone scan and SPECT/CT appearances were in keeping with osteopetrosis.
Figure 1: (a) X-ray of spine shows dense and sclerosis at the margins of the vertebral bodies in alternating parallel sclerotic and lucent bands (sandwich vertebrae or "rugger-jersey" spine). (b) Dual-energy X-ray absorptiometry scan shows dense sclerosis at the margins of the vertebral bodies and the T-score was high at +6.5 (b and c). On computed tomography (CT) component of single-photon emission computed tomography/CT, there is dense sclerosis at the margins of the vertebral bodies (bone-in-bone appearance) and within the pelvic bones (d and e)

Click here to view
Figure 2: 99mTc-methylene diphosphonate bone scan shows increased tracer uptake at the proximal ends of humeri and tibiae along with proximal and distal ends of femora. Linear uptake at the proximal femora and several lower ribs bilaterally is suggestive of fracture at these sites

Click here to view

   Discussion Top


Several different types of osteopetrosis have been described, distinguished by the pattern of inheritance - autosomal dominant, autosomal recessive, or X-linked. [1] [Table 1].
Table 1: Summary of pathogenesis and management of osteopetrosis[1-12]

Click here to view

Autosomal dominant osteopetrosis (ADO) is also known as Albers-Schφnberg disease after first being described in 1904. Typically in the mildest form of the disorder, affected individuals may show no symptoms. The incidence is 1:20000, and a mutation in the CLCN7 gene is responsible for 75% of ADO. [2] Due to its benign symptoms, ADO is usually discovered by accident when X-ray is done for another reason. Clinical manifestations become apparent in late childhood or adolescence; symptoms include: Multiple bone fractures, scoliosis, arthritis, and osteomyelitis.

Autosomal recessive osteopetrosis (ARO) has an incidence of 1:250000. CLCN7 gene was identified in 10-15% of ARO cases, and TCIRG1 gene in 50% of cases. [3] It is of a more severe form and usually happens in early infancy. Dense skull bones compress on nerves in the head and neck, resulting in vision loss, hearing loss, dental abnormalities and paralysis of facial muscles. Dense bones can also impair bone marrow function, causing haematological complications such as abnormal bleeding, anaemia and recurrent infections, which in turn results in hepatosplenomegaly.

Intermediate autosomal osteopetrosis (IAO) is a spectrum that ranges between severe ARO and mild ADO. The affected individual can have either autosomal-dominant or autosomal-recessive pattern inheritance. Signs become noticeable in childhood and include increased risk of bone fracture. In general, they do not have life-threatening bone marrow abnormalities, but calcifications in the brain can cause intellectual disability, and patients may also present with renal tubular acidosis.

X-linked osteopetrosis is rare and is due to mutation in the IKBKG gene. [4] It is characterized by lymphedema and anhidrotic ectodermal dysplasia. Individuals with this condition also have immunodeficiency, which allows severe and recurrent infections to develop.


Normal bone growth is regulated by a balance between bone formation by osteoblasts and bone resorption by osteoclasts. In osteopetrosis, gene mutations cause failure of the resorptive process and hence a remodeling imbalance. The exact mechanism is unknown, however deficiency of carbonic anhydrase II is noted in osteoclasts of affected patients. Carbonic anhydrases catalyze the formation of carbonic acid from carbon dioxide and water. Carbonic acid then dissociates to produce protons, which makes the resorption lacunae acidic. Absence of this enzyme causes defective hydrogen ion pumping, which reduces resorption by osteoclasts, as an acidic environment is required for dissociation of calcium hydroxyapatite from bone matrix. [3] Hence, bone resorption fails while there is continuous formation, forming excessive bone.


Diagnosis of osteopetrosis is clinical, based on history and physical examination showing bone defects. It also relies greatly on appearance of the skeleton radiographically [Table 1].

On plain radiographs, osteopetrosis can present as osteosclerosis or dense bones [Figure 1]a. Four classic features appear in radiographs of patients with ADO: (1) Diffuse sclerosis, affecting the skull, spine, pelvis and appendicular bones; (2) Metaphysic long bone defects known as "Erlenmeyer flask deformity," and characteristic lucent bands; (3) "bone-in-bone" appearance of the vertebrae and phalanges; and (4) sclerosis of skull base, pelvis and vertebral end plates, giving rise to "sandwich" vertebrae, and "rugger-jersey" spine. [2] The appearance on radiographs can further differentiate ADO into two subtypes. Type I shows pronounced sclerosis of the skull with enlarged thickness of the cranial wall, and type II shows more sclerosis at the base. [5]

Dual-energy X-ray absorptiometry is a method of measuring bone mineral density (BMD). It gives quantitative measures and shows elevation of BMD in patients with osteopetrosis [6] [Figure 1]b. It is considered a safe and noninvasive means of assessing disease progression and response after treatment.

Radiotracers have also been used to assess osteopetrosis. 99m Tc-sulfur colloid scintigraphy is best used to show bone marrow distribution of the disease. 99m Tc-MDP is used to show uptake at multiple fracture sites and at splayed metaphyses of long bones. Elster et al. also showed that it is possible to use 99m Tc-MDP to correlate the appearance of bone marrow stores with advancing age in children [7] [Figure 2]a. Further, the bone scan is useful to assess fracture sites and SPECT/CT, help in accurate localisation, and to confirm or exclude any abnormal sites of increased metabolic activity.

99m Tc-human serum albumin (HSA), microspheres are used to demonstrate absence of bone marrow activity, hepatosplenomegaly and sites of extramedullary haematopoiesis, and may be helpful in monitoring effectiveness of therapy after treatment. [8]

Computed tomography scan often shows increased area of bone density [Figure 1]d and e, "bone-in-bone" appearance in the vertebrae and phalanges, and sometimes focal sclerosis of skull base, pelvis and vertebral end plates, giving rise to "sandwich" vertebrae, and "rugger-jersey" spine [Figure 1]d.

Magnetic resonance imaging (MRI) is used in more severe cases of osteopetrosis to determine the amount of remaining marrow space. The characteristic appearance shows alternating lack of signal with signal similar to intervertebral discs in the marrow, giving a "stepladder appearance." There may also be "hair on end" appearances that reflect marked haematopoietic activity. [7] A recent MRI study with 47 affected patients showed sclerosis and thickening of the calvaria in all patients. However, there were two features that showed exclusively in patients with ARO - stenosis of the internal carotid and vertebral arteries, and extramedullary haematopoiesis, which is probably due to the earlier age of onset in ARO and greater severity in this form of the disease. [9]


Treatment of this disease is largely based on symptoms. [2] While some may be asymptomatic, many of these patients require orthopaedic surgery at some point in their lives for fractures. The only definitive cure for osteopetrosis is bone marrow transplant, [10] but other medications are also used in nonsurgical management. Vitamin D supplements can be used to stimulate dormant osteoclasts, increasing bone resorption. Corticosteroids are recommended to stimulate bone resorption and to treat anaemia, [11] along with erythropoietin. Gamma interferon has also been shown to be effective in improving immunity, increasing bone resorption and enlarging marrow space. [12]

   References Top

Balemans W, Van Wesenbeeck L, Van Hul W. A clinical and molecular overview of the human osteopetroses. Calcif Tissue Int 2005;77:263-74.  Back to cited text no. 1
Stark Z, Savarirayan R. Osteopetrosis. Orphanet J Rare Dis 2009;4:5.  Back to cited text no. 2
Frattini A, Pangrazio A, Susani L, Sobacchi C, Mirolo M, Abinun M, et al. Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis. J Bone Miner Res 2003;18:1740-7.  Back to cited text no. 3
Döffinger R, Smahi A, Bessia C, Geissmann F, Feinberg J, Durandy A, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet 2001;27:277-85.  Back to cited text no. 4
Bollerslev J, Andersen PE Jr. Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis. Bone 1988;9:7-13.  Back to cited text no. 5
Kaste SC, Kasow KA, Horwitz EM. Quantitative bone mineral density assessment in malignant infantile osteopetrosis. Pediatr Blood Cancer 2007;48:181-5.  Back to cited text no. 6
Elster AD, Theros EG, Key LL, Stanton C. Autosomal recessive osteopetrosis: Bone marrow imaging. Radiology 1992;182:507-14.  Back to cited text no. 7
Thelen MH, Eschmann SM, Moll-Kotowski M, Dopfer R, Bares R. Bone marrow scintigraphy with technetium- 99m anti-NCA-95 to monitor therapy in malignant osteopetrosis. J Nucl Med 1998;39:1033-5.  Back to cited text no. 8
Curé JK, Key LL, Goltra DD, VanTassel P. Cranial MR imaging of osteopetrosis. AJNR Am J Neuroradiol 2000;21:1110-5.  Back to cited text no. 9
Gerritsen EJ, Vossen JM, Fasth A, Friedrich W, Morgan G, Padmos A, et al. Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group. J Pediatr 1994;125:896-902.  Back to cited text no. 10
Mohn A, Capanna R, Delli Pizzi C, Morgese G, Chiarelli F. Autosomal malignant osteopetrosis. From diagnosis to therapy. Minerva Pediatr 2004;56:115-8.  Back to cited text no. 11
Key LL Jr, Rodriguiz RM, Willi SM, Wright NM, Hatcher HC, Eyre DR, et al. Long-term treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med 1995;332:1594-9.  Back to cited text no. 12


  [Figure 1], [Figure 2]

  [Table 1]

This article has been cited by
1 Progressive skeletal defects caused by Kindlin3 deficiency, a model of autosomal recessive osteopetrosis in humans
Tejasvi Dudiki, Daniel W. Nascimento, Lauren S. Childs, Swetha Kareti, Charlie Androjna, Irina Zhevlakova, Tatiana V. Byzova
Bone. 2022; : 116397
[Pubmed] | [DOI]
2 An Extremely Rare, Atypical and Genetically-undetermined Form of Osteopetrosis
Cecilia Tetta, Marco Focaccia, Lea Bono, Eugenio Rimondi, Paolo Spinnato
Current Medical Imaging Formerly Current Medical Imaging Reviews. 2021; 17(8): 1036
[Pubmed] | [DOI]
3 Radiographic imaging, densitometry and disease severity in Autosomal dominant osteopetrosis type 2
Lauren M. Ladd, Erik A. Imel, Paul J. Niziolek, Ziyue Liu, Stuart J. Warden, Yun Liang, Michael J. Econs
Skeletal Radiology. 2021; 50(5): 903
[Pubmed] | [DOI]
4 Diagnosis and management of pediatric metabolic bone diseases associated with skeletal fragility
Nipith Charoenngam, Muhammet B. Cevik, Michael F. Holick
Current Opinion in Pediatrics. 2020; 32(4): 560
[Pubmed] | [DOI]
5 Magnetic Resonance Imaging Diagnosis of Osteopetrosis in a Child Presenting with Blindness
Vijinder Arora, Nilanshu Kataria
Indian Journal of Musculoskeletal Radiology. 2019; 1: 64
[Pubmed] | [DOI]
6 Bone Scintigraphy: A Review of Technical Aspects and Applications in Orthopedic Surgery
John W. Krumme, Madelyn F. Lauer, Justin T. Stowell, Nebiyu M. Beteselassie, Suhel Y. Kotwal
Orthopedics. 2019; 42(1)
[Pubmed] | [DOI]
NS S Nikolaev, LV V Borisova, SN N Didichenko, NV V Bezludnaya, IB B Bashkova, EA A Lyubimov
Science and Innovations in Medicine. 2017; 2(4): 65
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded240    
    Comments [Add]    
    Cited by others 7    

Recommend this journal