Under the term osteopetrosis, the medical profession refers to a hereditary disease, the exact cause of which is still unknown. A degradation disorder of the bone is characteristic of osteopetrosis. The disturbance of bone resorption subsequently causes a pathological accumulation of the bone matrix. Osteopetrosis is hardly curable; there is also no specific therapy that specifically treats the cause, so 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 a direct inheritance has not taken place, but the affected person can very well pass on the osteopetrosis. Due to the hereditary underactivity of the osteoclasts (these are the cells that break down bone), the genetic disease develops. If the medical doctor has diagnosed osteopetrosis, it is divided into two main groups:
- Thus, 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 renaul-tubular acidosis, infantile malignant osteopetrosis).
For the course of further treatments and also the prognosis, it is essential that the physician divides osteopetrosis into its type.
Causes
The causes of the gene mutation are unclear so far; however, physicians have found out which defects are present in which areas. Thus, in autosomal recessive osteopetrosis, positions TCIRGI1, OSTM1, SNX10, and/or CLCN7 are affected in osteoclast-rich forms, and positions TNFRSF11A (RANK) and/or TNFSF11 (RANKL) are affected in osteoclast-poor forms. If autosomal recessive osteopetrosis with renal tubular acidosis is present, the mutation is on CAII; if autosomal dominant osteopetrosis is present (type 1), the mutation is on LRP5; and if type 2 is present, the mutation is on CLCN 7.
Symptoms, complaints, and signs
As the medullary spaces shrink and extramedullary hematopoiesis then occurs, the microarchitecture in the bone is destroyed. The destruction subsequently leads to bone instability, putting affected individuals at increased risk of suffering fractures. Furthermore, the constant build-up of bone matrix, with no degradation activity, results in hypocalcemia. Due to the matrix proliferation, constriction also occurs in the skull bone, so that the optic nerves (in the area of the canales optici) are pinched. The compression sometimes leads to degeneration of the nerves, so that the affected person may go blind. In some cases, pinched cranial nerves have also been reported (such as vestibulocochlear nerve, facial nerve), so that the affected person suffered from functional deficits. However, blindness as well as functional deficits are among the rare symptoms of osteopetrosis; the focus is on the problem of bone stability and the associated fracture frequency.
Diagnosis and disease progression
Osteopetrosis can be diagnosed using imaging techniques (such as an x-ray) – in combination with the clinical clinical picture. For any bone marrow sclerosis that has occurred to be confirmed, a bone punch biopsy is advised. On the X-ray images, the physician recognizes not only sclerosis 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 striations 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 marked hypocalcemia. Due to the bony substitute that forms in the bone marrow, there is on the one hand an increased susceptibility to infections and on the other hand anemia may occur. In the course of diagnosis, however, the physician must be able to exclude 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 already in the first years of life of the affected person.The first symptoms can be seen just a few weeks after birth. If autosomal recessive osteopetrosis is not treated, the prognosis is negative. There is only a chance of cure in the context of a bone marrow transplant. In type I of autosomal dominant osteopetrosis, the main focus is on the skull base, while in type II the “sandwich vertebrae” are characteristic. Both forms cause initial symptoms during the growth spurt. Causative treatments are not available for types I and II, so that mainly the symptoms are treated. This means that – as with autosomal recessive osteopetrosis – there is no definitive cure.
Complications
As a result of osteopetrosis, the risk for fractures and broken bones primarily increases. Because of extramedullary (“located outside the medulla”) hematopoiesis, there is increased liver and spleen enlargement, decreased immune defenses, seizures, and nerve damage. The latter mainly affect the cranial nerves and can subsequently lead to blindness and other deficits. In individual cases, osteopetrosis can lead to damage to the lower jaw and the periodontium. In addition, cosmetic problems occur, which in the course can lead to psychological complaints. In severe cases, osteopetrosis is fatal. A number of side effects and interactions may occur during drug treatment of osteopetrosis. Vitamin D preparations can cause nausea and vomiting, as well as muscle weakness and joint pain, among other things. The active ingredient glucocorticoid can cause growth disorders, glaucoma, cataracts, and psychological changes such as sleep disturbances and restlessness. There are also risks associated with the frequently used bone marrow transplantation. Complications such as rejection of the bone marrow from the recipient organism often occur during the surgical procedure. As a result, skin, liver, and intestinal damage may occur, sometimes exacerbating the original osteopetrosis.
When should you go to the doctor?
Anyone who suffers repeated fractures or suddenly notices vision problems should consult their primary care physician. The symptoms indicate osteopetrosis, which must be diagnosed by a specialist. In case of suspicion, it is best to consult the orthopedist. Medical advice is required if the symptoms occur in connection with other malformations or bone diseases. Since it is a hereditary disorder, the disease can be detected in the early stages by genetic testing. Parents should consult the pediatrician in case of dysfunction of the child’s locomotor system. In case of complaints of the eyes, the ophthalmologist must be consulted. During treatment, physiotherapists and sports physicians are also involved and support the patient over a long period of time. Parents should consult with the appropriate physicians during therapy. If the child falls or is otherwise injured, the emergency medical services should be called. In the event of severe discomfort, the emergency medical service must also be contacted so that the child can be helped immediately after the fall. After initial treatment by the emergency physician, the patient must be examined at the hospital. There, any fractures or sprains will be diagnosed and treated. Osteopetrosis can be treated relatively well, but due to the high risk of fractures, serious injuries can always occur and require treatment.
Treatment and therapy
In the context of osteopetrosis, there is no causal therapy. For this reason, the physician must treat the symptoms of the patient and thus ensure that the quality of life can be increased. As part of the treatment, glucocorticoids as well as interferons are administered to bring about an improvement in the symptoms and discomfort. The only effective therapy is bone marrow transplantation. By means of this variant there is a possibility of normalization of osteoclasts due to hematopoietic stem cells. However, bone marrow transplantation is only possible in autosomal recessive osteopetrosis; all other types have no definitive cure, so the therapy aims to alleviate the symptoms and discomfort and to increase the quality of life of the affected person.
Outlook and prognosis
In marble bone disease or osteopetrosis, the outlook for a cure is usually poor.This diagnosis applies especially if this disease remains untreated. In most cases, there is a hereditary underactivity of the so-called osteoclasts. This subsequently causes unregulated bone formation. So far, the only treatment option is a bone marrow transplant. This is the only way to restore sufficient osteoclast formation. Osteoclasts are cells that break down bone. However, transplantation carries high risks, namely calcemia as a consequence. Differences in the course of the disease are seen in the autosomal recessive and autosomal dominant forms of the disease. Autosomal recessive osteopetrosis usually develops in early childhood. It sometimes also develops postnatally as infantile malignant osteopetrosis. Mild clinical pictures are also known. These may show overlap with dominant osteopetrosis. Without symptomatic treatment and bone marrow transplantation, the outlook is bleak. Autosomal dominant osteopetrosis (ADOI) usually presents as generalized osteosclerosis of the skull base, or as an Albers-Schönberg variant (ADOII) with “sandwich vertebrae”. This form of the disease manifests itself only in adolescence. The courses of both are different. In one variant, the bones become increasingly stable. In the other, they break more easily. In addition, complications may occur. There is currently nothing more than symptomatic therapy.
Prevention
Due to the fact that so far no causes have been found for which reason osteopetrosis occurs, preventive measures are not possible.
Aftercare
In most cases of osteopetrosis, patients have very few and limited measures of direct aftercare available. First and foremost, a rapid and, above all, an early diagnosis of the disease should be made so that complications or other complaints do not arise in the further course. The earlier a doctor is consulted, the better the further course of the disease usually is, so that a doctor should be contacted at the first signs and symptoms. Most patients are dependent on taking various medications for osteopetrosis. The correct dosage and regular intake of the medication must always be observed in order to permanently limit the symptoms. Furthermore, the affected person should contact a doctor if side effects or uncertainties arise. Sometimes psychological support can be helpful, especially in preventing the development of depression. It is also very important to support the affected person in their everyday life in order to increase their quality of life. In some cases, osteopetrosis also reduces the quality of life of the affected person.
What you can do yourself
In cases of osteopetrosis, the most important self-help measure is to regularly perform the physical exercises recommended by the doctor and otherwise take it easy on the affected bones. Comprehensive physical therapy can at least slow the progression of the disease. In addition, sport improves well-being and thus contributes to an improvement in the quality of life. Affected individuals should also change their diet. It is advisable to avoid foods with too much salt, as these can lead to an increase in osteoclasts. After a bone marrow transplant, rest is the order of the day. The osteopetrosis patient should refrain from strenuous physical activity for one to two weeks and even beyond that. If this does not relieve the symptoms, a further visit to the doctor is recommended. Patients can also talk to an alternative medical practitioner about another treatment. Both massage and acupuncture are discussed as effective adjunctive measures for osteopetrosis. However, in the case of the condition, which steps are useful depends largely on the course of the disease and the accompanying circumstances. Therefore, the accompanying measures should be discussed with the responsible orthopedist, similar to the therapy itself.
