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Res�menes Epistemonikos

Mewave 2016;16(Suppl 1):e6406 doi: 10.5867/medwave.2016.6406

�Es �til la instilaci�n de c�lulas madre de m�dula �sea al momento de la descompresi�n �sea en la osteonecrosis de cabeza femoral?

Is instillation of bone marrow stem cells at the time of core decompression useful for osteonecrosis of the femoral head?

Jorge Cabrolier, Marcelo Molina

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Abstract

Osteonecrosis of the femoral head leads to degeneration of the head and finally to osteoarthritis of the hip. Decompression is the most widely used treatment, but its effectiveness is limited. It has been proposed instillation of stem cells in addition to decompression, would lead to better results. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including two randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded instillation of bone marrow stem cells at the time of core decompression probably slows progression to osteoarthritis of the hip in patients with osteonecrosis of the femoral head and might reduce the need of subsequent surgeries. It is unclear whether it has any effect on the functionality because the certainty of the evidence is very low.

Problem

Osteonecrosis of the femoral head mainly affects adults between the third and sixth decade of life. It has multiple causes, but it is generally produced by a severe deficiency of blood flow leading to bone necrosis and subsequent collapse of the femoral head. In the absence of early intervention with intention to preserve the native joint, there is a high risk of developing osteoarthritis of the hip.

Decompression is the most widely used treatment for avascular necrosis of the femoral head, but its effectiveness is limited.

Use of mesenchymal stem cells from adult bone marrow, in addition to decompression, would promote bone formation and neovascularization, which could improve prognosis in early stages of osteonecrosis. However, there is controversy about whether its ability to improve joint function or to increase the time until requirement of total hip arthroplasty.

Methods

We used Epistemonikos database, which is maintained by screening more than 30 databases, to identify systematic reviews and their included primary studies. With this information, we generated a structured summary using a pre-established format, which includes key messages, a summary of the body of evidence (presented as an evidence matrix in Epistemonikos), meta-analysis of the total of studies, a summary of findings table following the GRADE approach and a table of other considerations for decision-making.

Key messages

Instillation of bone marrow stem cells at the time of core decompression in osteonecrosis of the femoral head probably slows progression to osteoarthritis and may reduce the need for subsequent surgeries.
It is unclear whether it has any effect on the functionality because the certainty of the evidence is very low.

About the body of evidence for this question

What is the evidence. See evidence matrix in Epistemonikos later	We found two systematic reviews [1],[2] which included seven primary studies [3],[4],[5],[6],[7],[8],[9], two of them [3],[4], corresponded to randomized controlled trials. This table and the summary in general are based on the latter.
What types of patients were included	One study [4] included patients between 18 and 55 years of age with osteonecrosis of one or both hips stages IC to IIC according to the ARCO ( Association Research Circulation Osseous) classification with risk factors such as trauma, steroid use, alcohol abuse, Caisson disease or idiopathic aetiology (some patients had more than one cause). The other randomized study [3] included patients without specifying age with osteonecrosis of one or both femoral heads ARCO stage I or II (without subtype specification), of varied aetiologies including traumatic, steroid use, alcohol abuse, Cushing's disease, pregnancy induced and idiopathic.
What types of interventions were included	Both studies included as intervention stem cells derived from bone marrow injected into the necrotic area through a tunnel of decompression. One study [3] used a concentrate of mononuclear cells derived from bone marrow obtained from iliac crest, in doses of 5x10⁸ cells (total mononuclear cell count). The second study [4] used mesenchymal stem cells obtained after two weeks of culture of concentrate mononuclear cells derived from bone marrow obtained from the sub trochanteric region of the affected femur at doses of 2x10⁶ cells (total mesenchymal stem cell count). Both studies compared against core decompression alone
What types of outcomes were measured	Harris Hip Score, progression to a more advanced stage according to ARCO classification, volume of necrotic area assessed by magnetic resonance, progression and need of vascularized bone graft or conversion to total hip arthroplasty.

We found three systematic reviews [5], [6], [7], including 14 studies reported in 21 references [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. Eight studies correspond to randomized controlled trials (15 references [9], [10], [11], [12], [13], [14], [16], [17], [19], [21], [22], [23], [24], [26], [27]). This table and the summary in general are based on the latter. One study [15] did not contribute data to any of the outcomes of interest.

Summary of findings

Information on the effects of instillation of stem cells at the time of core decompression in osteonecrosis of the femoral head is based on two randomized controlled trials [3],[4] including 148 cases in 133 patients. Information about progression, conversion to bone graft and conversion to total hip arthroplasty are based on one study [4]. The functionality is based on a second study [3].

Instillation of bone marrow stem cells at the time of core decompression probably slows progression in early-stage osteonecrosis of the femoral head. The certainty of the evidence is moderate.
Instillation of bone marrow stem cells at the time of core decompression in osteonecrosis of the femoral head might decrease conversion to vascularized bone graft. The certainty of the evidence is low.
Instillation of bone marrow stem cells at the time of core decompression in osteonecrosis of the femoral head might decrease the conversion to total hip arthroplasty. The certainty of the evidence is low.
It is unclear whether bone marrow stem cells instillation upon core decompression in osteonecrosis of femoral head improves functionality because the certainty of the evidence is very low.

Other considerations for decision-making

To whom this evidence does and does not apply

This evidence applies to adult patients with diagnosis of osteonecrosis of femoral head of traumatic or atraumatic aetiology, in ARCO stages I or II.

About the outcomes included in this summary

This summary considers functionality, progression to more advanced ARCO stages (III or IV ), and subsequent need of vascularized bone graft or need of total hip arthroplasty, outcomes considered critical for decision making by the authors of this summary.

Balance between benefits and risks, and certainty of the evidence

Since there is uncertainty about the benefits of stem cell therapy for osteonecrosis of femoral head, it is not possible to make an adequate risk/benefit balance .
If the observed benefit were real, it would be an intervention with a very favorable risk/benefit ratio.

Resource considerations

Stem cells therapy currently represents a high cost and limited access intervention, so it is likely that patients and physicians would not be inclined to use it, even more considering the existent uncertainty about its effects.
It is not possible to determine whether it is a cost effective intervention that would generate long-term savings, because the certainty of the evidence regarding their benefits is poor.

Differences between this summary and other sources

The key messages of our summary are partially consistent with the conclusions of the individual systematic reviews identified, which give a more optimistic conclusion, because of the weight given to observational studies included. They also highlight the proven benefits of stem cell therapy in preclinical studies.
Our summary is consistent with the main clinical guidelines [10],[11] concerning the treatment of osteonecrosis of femoral head, where the need for prospective studies with documentation of the initial stage of disease, progression and time to total hip arthroplasty is suggested.

Could this evidence change in the future?

The probability that future evidence change the key findings of this summary is high due to the limitations of the existing evidence .
There are multiple ongoing studies that could provide relevant information for this question.

How we conducted this summary

Using automated and collaborative means, we compiled all the relevant evidence for the question of interest and we present it as a matrix of evidence.

Follow the link to access the interactive version: Core decompression and stem cell instillation versus core decompression alone for early stage osteonecrosis of the femoral head

Notes

The upper portion of the matrix of evidence will display a warning of “new evidence” if new systematic reviews are published after the publication of this summary. Even though the project considers the periodical update of these summaries, users are invited to comment in Medwave or to contact the authors through email if they find new evidence and the summary should be updated earlier. After creating an account in Epistemonikos, users will be able to save the matrixes and to receive automated notifications any time new evidence potentially relevant for the question appears.

The details about the methods used to produce these summaries are described here http://dx.doi.org/10.5867/medwave.2014.06.5997.

Epistemonikos foundation is a non-for-profit organization aiming to bring information closer to health decision-makers with technology. Its main development is Epistemonikos database (www.epistemonikos.org).

These summaries follow a rigorous process of internal peer review.

Conflicts of interest
The authors do not have relevant interests to declare.

Licencia Creative Commons

Esta obra de Medwave est� bajo una licencia Creative Commons Atribuci�n-NoComercial 3.0 Unported. Esta licencia permite el uso, distribuci�n y reproducci�n del art�culo en cualquier medio, siempre y cuando se otorgue el cr�dito correspondiente al autor del art�culo y al medio en que se publica, en este caso, Medwave.

Edici�n Julio 2022

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