The term osteopetrosis is used by doctors to describe a hereditary disease whose exact cause is still unknown. Bone degradation is characteristic of osteopetrosis. The disruption of bone resorption subsequently leads to a pathological accumulation of the bone matrix. Osteopetrosis is hardly curable; there is also no special therapy that specifically treats the cause, so that only symptom-related treatment is given.
What is osteopetrosis?
Osteopetrosis, also known as marble bone disease, osteopetrosis, Alberts -Schönberg disease, is usually inherited. There is also the possibility of a spontaneous mutation, so that direct inheritance has not taken place, but the affected person can very well pass on the osteopetrosis. See theinternetfaqs for Scabies Basics.
Due to the hereditary underfunction of the osteoclasts (these are the bone-degrading cells), the genetic disease arises. If the doctor has diagnosed osteopetrosis, it is divided into two main groups:
- There are the autosomal dominant forms of type 1 (ADOI) and type 2 (ADOII, also known as Albers-Schönberg disease)
- As well as the autosomal recessive forms (osteopetrosis with renal tubular acidosis, infantile malignant osteopetrosis).
For the course of further treatments and also the prognosis, it is essential that the doctor divides the osteopetrosis into its type.
The causes of the gene mutation are so far unclear; However, doctors have found out which defects are present in which areas. In the context of autosomal recessive osteopetrosis, the positions TCIRGI1, OSTM1, SNX10 and/or CLCN7 are affected in the osteoclast-rich forms and the positions TNFRSF11A (RANK) and/or TNFSF11 (RANKL) in the osteoclast-poor forms.
Autosomal recessive osteopetrosis with renal tubular acidosis is an alteration on CAII, autosomal dominant osteopetrosis (type 1) is an alteration on LRP5, and type 2 is a mutation on CLCN7.
Symptoms, Ailments & Signs
As the medullary spaces shrink and then extramedullary blood formation occurs, the microarchitecture in the bone is destroyed. The destruction subsequently leads to bone instability, so that those affected are at an increased risk of suffering fractures. Furthermore, the constant build-up of the bone matrix, with no degradation activities taking place, leads to hypocalcaemia.
Due to the increase in matrix, there is also narrowing in the skull bones, so that the optic nerves (in the area of the optic canals) are pinched. The compression sometimes leads to degeneration of the nerves, which can lead to blindness in the affected person. In some cases, pinched cranial nerves were also reported (e.g. vestibulocochlear nerve, facial nerve), so that the affected person suffered from functional deficits.
However, blindness and functional deficits are among the rare symptoms of osteopetrosis; The focus is on the problem of bone stability and the associated fracture frequency.
Diagnosis & course of disease
Osteopetrosis can be diagnosed using imaging methods (such as an X- ray) – in combination with the clinical symptoms. Bone punch biopsy is recommended to confirm bone marrow sclerotherapy. On the X-ray images, the doctor not only recognizes a sclerotherapy of the bone matrix, but also a strong compression of the same.
This is the so-called “sandwich vertebra”, a 3-layered vertebral body. Metaphyseal and diaphyseal streaks can also be seen, which were also responsible for the formation of the term “marble bone”. Bone density is also increased on CT. Blood tests usually show pronounced hypocalcemia.
Due to the bony replacement that forms in the bone marrow, there is an increased susceptibility to infection or anemia can occur. As part of the diagnosis, however, the doctor must be able to rule out other diseases; these include melorheostosis, sclerostosis, pycnodysostosis, Engelmann syndrome (also known as progressive diaphyseal dysplasia) and Pyle syndrome. All of these diseases have a similar clinical picture.
The course of autosomal dominant or recessive osteopetrosis is different. Autosomal recessive osteopetrosis manifests itself in the first years of the affected person’s life. The first symptoms can be seen just a few weeks after birth. If autosomal recessive osteopetrosis is not treated, the prognosis is negative. There are only chances of recovery as part of a bone marrow transplant.
In type I autosomal dominant osteopetrosis, the main focus is on the base of the skull, while in type II the “sandwich vertebrae” are characteristic. Both forms cause initial symptoms during the growth spurt. Causal treatments are not available for types I and II, so the symptoms are primarily treated. This means that – as with autosomal recessive osteopetrosis – there is no definitive chance of recovery.
As a result of osteopetrosis, the risk of fractures and broken bones increases in the first place. Due to the extramedullary (“located outside of the marrow”) blood formation, liver and spleen enlargement, a reduced immune system, seizures and nerve damage occur more frequently. The latter primarily affect the cranial nerves and can subsequently lead to blindness and other symptoms.
In individual cases, osteopetrosis can lead to damage to the lower jaw and the periodontium. In addition, cosmetic problems arise, which can lead to psychological problems in the course of time. In severe cases, osteopetrosis is fatal. A number of side effects and interactions can occur when treating osteopetrosis with medication. Vitamin D supplements can cause nausea and vomiting, as well as muscle weakness and joint pain, among other things.
The active substance glucocorticoid can lead to growth disorders, glaucoma, cataracts and psychological changes such as sleep disorders and restlessness. There are also risks associated with the frequently used bone marrow transplant. Complications such as the rejection of the bone marrow from the recipient organism often occur during the surgical procedure. As a result, skin, liver and intestinal damage can occur, which sometimes exacerbates the original osteopetrosis.
When should you go to the doctor?
Anyone who suffers repeated fractures or suddenly notices visual problems should consult their family doctor. The symptoms indicate osteopetrosis, which must be diagnosed by a specialist. If there is any suspicion, it is best to see an orthopedist. Medical advice is required if the symptoms occur in connection with other malformations or bone diseases.
Because it is an inherited condition, genetic testing can detect the condition in its early stages. Parents should consult the pediatrician in the event of functional disorders of the child’s musculoskeletal system. If there are problems with the eyes, the ophthalmologist must be consulted. Physiotherapists and sports physicians are also involved during the treatment and support the patient over a long period of time.
Parents should consult the responsible doctors during therapy. If the child falls or is otherwise injured, emergency services should be called. In the case of severe symptoms, the medical emergency service must also be contacted so that the child can be helped immediately after the fall. After the first aid by the emergency doctor, the patient must be examined in the hospital. Any fractures or sprains are identified and treated there. Osteopetrosis can be treated relatively well, but the high risk of fractures can lead to serious injuries that need to be treated.
Treatment & Therapy
There is no causal therapy for osteopetrosis. For this reason, the physician must treat the patient’s symptoms and thus ensure that the quality of life can be improved. Glucocorticoids and interferons are administered as part of the treatment, which are intended to improve the symptoms and symptoms.
The only truly effective therapy is based on bone marrow transplantation. By means of this variant there is a possibility that the osteoclasts, due to the hematopoietic stem cells, will normalize. However, bone marrow transplantation is only possible in autosomal recessive osteopetrosis; all other types do not have a definitive chance of recovery, so the therapy aims to relieve the symptoms and discomfort and to improve the quality of life of the person affected.
Outlook & Forecast
In the case of marble bone disease or osteopetrosis, the prospects for a cure are usually poor. This diagnosis is especially true if this condition is left untreated. In most cases, there is a hereditary underfunction of the so-called osteoclasts. This leads to unregulated bone formation.
So far, the only treatment option is a bone marrow transplant. This is the only way that sufficient osteoclasts can form again. Osteoclasts are bone-degrading cells. However, the transplantation involves high risks, namely calcaemia as a result.
Differences in the course of the disease can be found in the autosomal recessive and the autosomal dominant form of the disease. Autosomal recessive osteopetrosis usually develops in early childhood. It sometimes develops after birth as infantile malignant osteopetrosis. Milder clinical pictures are also known. These can show overlaps with the dominant osteopetrosis. Without symptomatic treatment and a bone marrow transplant, the outlook is bleak.
Autosomal dominant osteopetrosis (ADOI) is usually present as generalized osteosclerosis of the skull base, or as an Albers-Schönberg variant (ADOII) with “sandwich vertebrae”. This form of the disease does not manifest itself until adolescence. The forms of both are different. In one variant, the bones become more and more stable. The other breaks more easily. In addition, complications can arise. There is currently no more than symptomatic therapy.
Due to the fact that so far no causes have been found for which reason osteopetrosis occurs, preventive measures are not possible.
In most cases, patients with osteopetrosis have only very few and limited direct follow-up measures available. First and foremost, the disease should be diagnosed quickly and, above all, at an early stage, so that complications or other symptoms do not arise later on. The earlier a doctor is consulted, the better the further course of the disease, so that a doctor should be contacted as soon as the first signs and symptoms appear.
Most patients with osteopetrosis are dependent on taking various medications. It is always important to ensure that the dosage is correct and that the medication is taken regularly in order to permanently limit the symptoms. Furthermore, the person concerned should contact a doctor if side effects or ambiguities arise.
Psychological support can sometimes be helpful, which can prevent the development of depression in particular. It is also very important to support those affected in their everyday lives in order to improve their quality of life. In some cases, osteopetrosis also reduces the sufferer’s quality of life.
You can do that yourself
For osteopetrosis, the most important self-help measure is to regularly do the physical exercises recommended by your doctor and otherwise rest the affected bones. Comprehensive physiotherapy can at least slow down the progression of the disease. In addition, sport improves well-being and thus contributes to an improvement in the quality of life. Affected people should also change their diet. It is advisable to avoid foods with too much salt, as these can lead to an increase in osteoclasts.
Rest after a bone marrow transplant. Osteopetrosis patients should not exert themselves for one to two weeks and should also initially refrain from strenuous physical activities. If this does not alleviate the symptoms, a further visit to the doctor is recommended.
Patients can also talk to an alternative health practitioner about another treatment. Both massage and acupuncture are discussed as effective accompanying measures for osteopetrosis. Which steps make sense in the case of the ailment, however, depends largely on the course of the disease and the accompanying circumstances. For this reason, the accompanying measures should be discussed with the responsible orthopaedist in the same way as the therapy itself.