Background
Formation of lamellar bone in non-osseus tissue is a pathological process called heterotopic ossification (HO). This can occur in muscle or connective tissue as a result of trauma, surgery, fractures, neurological injury or genetic mutations (fibrodysplasia ossificans progressiva, Albright’s hereditary osteodystrophy). It causes major clinical burdens due to limitation of motion, persistent pain and nerve entrapement [
1‐
4]. So far morphometric data on morphometric indices like porosity, tissue mineral density, and trabecular volume is fragmentary for human samples and immunological data are rarely available. Skeletal muscle tissue has a wide capacity for regenaration by myogenic stem cells in combination with mesenchymal stromal cells. It is not clear which factors induce enchondral bone formation during this process. Some studies have proposed endothelial or brown adipogenic cells as a or the source for HO. The reciprocal interactions between bone and the immune system have become more the subject of increased attention in recent years and the so called osteoimmunology describes cytokine induces bone resorption and inflammatory induced ossification [
5‐
14].
Neurogenic HO induced by spinal cord or traumatic brain injury is described but detailed characteristion of immunologigal and morphologic changes are hardly available. It is the aim of this study to analyse the morphology and immunological status of patients with heterotopic ossification compared to individual healthy persons [
15].
Discussion
A neurogenic heterotopic ossification is a serious complication of traumas or disorders of the central nervous system observed in 20% of patients with this condition [
2]. The hip and elbow joints affected predominantly are with severe pain, loss of movement and nerve compression syndromes. In addition, complications of the urinary tract system and pressure ulcers may arise in this disease [
1‐
4]. In addition to conservative therapy with NSAIDs or bisphosphonates, surgical resection is indicated, with local recurrence being described.Neurogenic heterotopic ossification is characterized by ectopic bone formation in the soft tissue and muscle tissue around large joints, especially the hip and elbow joints. The severity of the HO depends on the severity of the brain damage. In the initial stage, NHO is difficult to diagnose and can also be interpreted as phlebitis, arthritis or cellulitis in a differential diagnosis, which often leads to a treatment delay. It is then necessary to take care of the hygiene in the case of concomitant diseases and complications as well as, for example, pressure ulcers, urinary tract infections or pneumonia [
1‐
5].
As a rule, surgical resection occurs within the first year after the occurrence of the disease, whereby the indication for the operation is indicated on the one hand by the size of the ossification, on the other also by pain and possible compression of nerves or blood vessels.
Good preoperative planning is important to avoid the potential complications such as infection, fracture, recurrent hemorrhage and nerve injury [
2,
20,
21].
The time should be chosen so that the ossification is mature, but not yet so great that the complication probability becomes more frequent. Setting the right time for resection is not always easy, especially given the recurrence probability determined by the severity of brain damage. Likewise, too late a resection is bad for the adjacent joint, since this it is then stiffened and subsequent mobilization is made more difficult. There are different reports in the literature such as a series with 20 hips and another with 29 patients, with an improvement in the scope of movement in both studies [
21,
22].
The pathophysiology of the NHO is not fully understood. However, there are 3 causes (traumatic, genetic, neurogenic) that can trigger the formation of the HO by activating stem cells for proliferation and differentiation [
23]. In these patients, humoral factors can be altered; the exact relationship between the nervous system and the bone is not fully understood. It has been shown that some factors such as vasoactive peptides, neurotransmitters and the vasoactive substance can be altered [
24‐
27]. There are some limitations in this study, one is the limited number of patients and another the descriptive concept. But our findings should induce other groups to initiate studies on this topic to get more information on the involvement of the immune system in HO.
In our study it is shown that immunological distribution in heterotopic ossification is altered compared to healthy subjects, this might reflect an immunological participation in the development of this entity. The result is tissue formation with a low bone volume fraction. Morphometric parameters additionally show that the disordered bone deposition in HO, e.g. of reactive woven bone, produces bone tissue that is characterized by a decrease in bone strength due to a low degree of mineralization and anisotropy. Further studies are needed to understand the mechanisms which induce HO.
Conclusions
This work shows altered immunological distribution that is accompanied by a low decrease in bone volume fraction and tissue mineral density in the heterotopic ossification sample compared to normal bone. Compared to healthy subjects, this might reflect an immunological participation in the development of this entity.
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