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Concomitant presentation of multiple vertebral and peripheral osteonecrosis

in a HIV-infected patient

Article in Joint Bone Spine · January 2012

DOI: 10.1016/j.jbspin.2011.12.002 · Source: PubMed

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332 Letters to the editor / Joint Bone Spine 79 (2012) 323–334

Table 2
Frequencies of alleles and genotypes of tumor necrosis factor receptor-associated factor 1 gene complement 5 (TRAF1/C5) rs10818488 single nucleotide polymorphism (SNP)
in rheumatoid arthritis (RA) and healthy controls.

SNP Genotype/allele RA cases n = 108 (%) Controls n = 161 (%) ␹2 P value OR (95% CI)

TRAF1/C5 rs10818488 AA 29 (26.8) 25 (15.5)

AG 56 (51.8) 83 (51.5) 7.22 0.027
GG 23 (21.2) 53 (32.9)

A 114 (52.7) 133 (41.3) 1.59

G 102 (47.2) 189 (58.6) 6.85 0.008 (1.11–2.28)

HWE: Hardy-Weinberg equilibrium; P = 0.027 for genotype frequencies and P = 0.008 for allele frequencies; HWE RA cases (P = 0.67) and HWE controls (P = 0.42).

3. Discussion [4] Schmidt RE, Gessner JE. Fc receptors and their interaction with complement in
autoimmunity. Immunol Lett 2005;100:56–67.
[5] Kurreeman FA, Rocha D, Houwing-Duistermaat J, et al. European consortium on
In this report, we confirmed the positive association of rheumatoid arthritis families. Replication of the tumor necrosis factor receptor-
rs10818488 A allele with RA in Tunisian patients. Our results associated factor 1/complement component 5 region as a susceptibility locus
confirm those of Kurreeman et al., [2,5]. Our results confirms too for rheumatoid arthritis in a European family-based study. Arthritis Rheum
2008;58:2670–4.
those of Albers et al., [6]. Conversely, there was no association
[6] Albers HM, Kurreeman FA, Houwing-Duistermaat JJ, et al. The TRAF1/C5 region
detected for the TRAF1/C5 rs10818488 A allele with RA patients is a risk factor for polyarthritis in juvenile idiopathic arthritis. Ann Rheum Dis
from the UK samples [7] and in Slovak population [8]. Interest- 2008;67:1578–80.
ingly, allele rs10818488 G had increased the risk for RA in Japanese [7] Barton A, Thomson W, Ke X, et al. Re-evaluation of putative rheumatoid
arthritis susceptibility genes in the post-genome wide association study era
study [9], while it decreased the risk in the present study and in the and hypothesis of a key pathway underlying susceptibility. Hum Mol Genet
original studies [2,5,6]. Lack of correlation between these different 2008;17:2274–9.
ethnic groups should not necessarily be regarded as an absence of [8] Stark K, Rovenský J, Blazicková S, et al. Association of common poly-
morphisms in known susceptibility genes with rheumatoid arthritis in a
TRAF1/C5 polymorphism associations with RA disease, but it may Slovak population using osteoarthritis patients as controls. Arthritis Res Ther
reflect heterogeneity in the genetic susceptibility to this disorder. 2009;11:R70.
The TRAF1/C5 region was first identified as a susceptibility and [9] Nishimoto K, Kochi Y, Ikari K, et al. Association study of TRAF1-C5
polymorphisms with susceptibility to rheumatoid arthritis and sys-
severity factor for RA in a genome-wide and a candidate gene temic lupus erythematosus in Japanese. Ann Rheum Dis 2010;69:
approach [2,10]. The authors suggested that this SNP could have a 368–73.
functional impact on C5 synthesis. They reported that it encodes a [10] Plenge RM, Cotsapas C, Davies L, et al. Two independent alleles at 6q23 associ-
ated with risk of rheumatoid arthritis. Nat Genet 2007;39:1477–82.
potential binding site for a histone acetyl transferase EP300, which
regulates transcription via chromatin remodeling. In that absence Emna Fakhfakh Karray a,∗,b
of the A allele, the binding site to the transferase is disrupted, which Hanen Chalbi a
could disturb the transcriptional activation of the C5 gene [2]. Based Imen Ben Dhifallah a
on these data, we can hypothesize that patients with RA with the Leith Zakraoui b
A allele have relatively more C5 than those with the G allele. High Kamel Hamzaoui a
levels of C5 and therefore of C5a are a hallmark of inflammation in a Homeostasis and Cell Dysfunction Unit Research

RA and could explain the link between the A allele and RA. 99/UR/08-40, Medicine University Tunis El-Manar,
In prospect, we suggest to recruit a larger number of patients 15, rue Djebel-Lakdar, 1007 Tunis, Tunisia
and investigate other possible associations between TRAF1/C5 gene b Department of Rheumatology, Hopital Mongi Slim

polymorphisms with RA in Tunisian patients in order to elucidate La Marsa, Tunisia

the role of TRAF1/C5 gene in the pathogenesis of RA. ∗ Corresponding author. Tel.: +216 23 68 28 68;
fax: +216 70 93 81 02.
Disclosure of interest
E-mail address: [email protected]
(E. Fakhfakh Karray)
The authors declare that they have no conflicts of interest con-
cerning this article.
8 December 2011
Available online 28 January 2012
Acknowledgments doi:10.1016/j.jbspin.2011.12.003

We are particularly grateful to all the patients who participated

in these studies and we thank them sincerely. Many thanks for the Concomitant presentation of multiple vertebral and peripheral
medical staff of the Mongi Slim Hospital, particularly for A. Amari osteonecrosis in a HIV-infected patient
for her help. This work was supported by grants from the Ministère
de l’Enseignement et de la Recherche Scientifique, (DGRST), Tunisia.
a r t i c l e i n f o
References Keywords:
Vertebral osteonecrosis
[1] Huizinga TW, Amos CI, van der Helm-van Mil AH, et al. Refining the com- Kümmell’s disease
plex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 Multiple osteonecrosis
shared epitope for antibodies to citrullinated proteins. Arthritis Rheum
HIV infection
2005;52:3433–8.
Highly active antiretroviral therapy
[2] Kurreeman FA, Padyukov L, Marques RB, et al. A candidate gene approach iden-
tifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. PLoS Med
2007;4:e278 [Erratum in: PLoS Med. 2007 Dec;4(12):e358].
[3] Wajant H, Henkler F, Scheurich P. The TNF-receptor-associated factor family:
We report a case of multiple vertebral and peripheral
scaffold molecules for cytokine receptors, kinases and their regulators. Cell
Signal 2001;13:389–400. osteonecrosis in a HIV-infected patient treated with HAART.
 Letters to the editor / Joint Bone Spine 79 (2012) 323–334 333

1. Case report

In June 2010, a 43-year-old man presented with pain and

swelling of both ankles. At the age of 30, he was diagnosed of HIV
infection and was treated with HAART (tenofovir, emtricitabine,
lopinavir and ritonavir). Medical history included tobacco use,
chronic alcohol consumption, opioids and benzodiazepines abuse,
traumatic rib fractures, COPD and HCV infection. Physical exami-
nation was unrevealing except for diffuse swelling and tenderness
in both ankles with severe mobility limitation. Laboratory studies
showed elevated liver enzymes and a positive cryoglobulin test.
The HIV-1-RNA viral load remained undetectable and the CD4+ T
cell count was 375 cells/␮L. Plain X-rays showed only soft-tissue Fig. 2. Lateral thoracic spine radiograph (A) showing wedge compression fractures
in vertebral bodies D7, D8 and D9, with intravertebral vacuum cleft sign in D8 and D9
swelling without bony lesions, and the bone scintiscan revealed an
(arrows). Thoracic spine lateral (B) and coronal (C) CT showing increased kyphotic
osteogenic reaction in the joint lines of both ankles and basis of deformity and vacuum cleft phenomenon in vertebral bodies D5, D6 (arrow heads),
metatarsal bones 1, 2, 3 and 4. The MRI study revealed extensive D8 and D9 (arrows).
and multiple bone infarcts affecting the distal tibia, the calcaneus
and mid-foot bone elements bilaterally, right talus bone and left
first toe (Fig. 1). Treatment with indomethacin was unsuccessful.
Some months later, he complained of progressive functional limi- 2. Discussion
tation and pain at right shoulder. Plain X-rays showed collapse and
luxation of humeral head compatible with advanced osteonecrosis, Several causes of osteoporosis in this patient included
which was confirmed by MRI. long-term smoking, chronic alcoholism, chronic hepatitis (sec-
In February 2011, he was re-admitted because of respiratory ondary to HCV infection and alcohol ingestion), and prolonged
infection with bronchospasm. During admission, he suffered from corticosteroid treatment. HIV-infected patients are at increased
an accidental fall with subsequent development of severe back risk for osteonecrosis due to a higher prevalence of predisposing
pain, progressive kyphosis and worsening of the respiratory insuf- factors to low bone mineral density (e.g., corticosteroids, alcohol
ficiency requiring continuous oxygen therapy. Lateral thoracic consumption) as well as the effect of HIV infection itself and HAART
spine radiographs revealed anterior wedge compression fractures (tenofovir and protease inhibitors) [1–5]. Because peripheral and
in vertebral bodies D6, D7 D8 and D9, with intravertebral vac- vertebral osteonecrosis share risk factors and several of these occur
uum cleft sign in D8 and D9 (Fig. 2). A computed tomography simultaneously in HIV-infected patients [6], vertebral osteonecro-
(CT) scan disclosed fractures of the vertebral bodies from D5 to sis should be considered in patients with history of peripheral
D9 without posterior wall involvement, presence of gas inside in osteonecrosis that develop vertebral compression fracture [7–9].
D5, D6, D8 and D9 compatible with vertebral osteonecrosis and We present a case of apparently concomitant peripheral and ver-
chronic collapse of superior endplates of D1, D4, D10 and D12 tebral osteonecrosis but whether both lesions rely on the same
(Fig. 2). mechanism remains unclear.
At follow-up, restrictive respiratory failure has not improved
and he continues on home oxygen therapy (16 hours/day). A
control CT scan showed multiple fractures of the tarsal bones and
Disclosure of interest
free bony fragments in the tibiotalar joints. The patient is restricted
to a wheelchair.
The authors declare that they have no conflicts of interest con-
cerning this article.

References

[1] Young B, Dao CN, Buchacz K, et al. Increased rates of bone fracture
among HIV-infected persons in the HIV Outpatient Study (HOPS) com-
pared with the US general population, 2000–2006. Clin Infect Dis 2011;52:
1061–8.
[2] Morse CG, Mican JM, Jones EC, et al. The incidence and natural history of
osteonecrosis in HIV-infected adults. Clin Infect Dis 2007;44:739–48.
[3] Gutiérrez F, Padilla S, Masiá M, et al. Osteonecrosis in patients infected with
HIV: clinical epidemiology and natural history in a large case series from Spain.
J Acquir Immune Defic Syndr 2006;42:286–92.
[4] Bonjoch A, Figueras M, Estany C, et al. High prevalence of and progression to low
bone mineral density in HIV-infected patients: a longitudinal cohort study. AIDS
2010;24:2827–33.
[5] Kaviani N, Bukberg P, Manessis A, et al. Iatrogenic osteoporosis, bilateral HIP
osteonecrosis, and secondary adrenal suppression in an HIV-infected man
receiving inhaled corticosteroids and ritonavir-boosted highly active antiretro-
viral therapy. Endocr Pract 2011;17:74–8.
[6] Monier P, McKown K, Bronze MS. Osteonecrosis complicating highly active
antiretroviral therapy in patients infected with human immunodeficiency virus.
Clin Infect Dis 2000;31:1488–92.
[7] Ma R, Chow R, Shen FH. Kummell’s disease: delayed post-traumatic osteonecro-
sis of the vertebral body. Eur Spine J 2010;19:1065–70.
[8] Young WF, Brown D, Kendler A, et al. Delayed post-traumatic osteonecrosis of a
vertebral body (Kummell’s disease). Acta Orthop Belg 2002;68:13–9.
Fig. 1. T1-weighted MRI sequence of left ankle (A) and foot (B) demonstrating [9] Javier RM, Moser T, Dietemann JL, et al. Multiple vertebral osteonecrosis. Joint
extensive infarcts in distal tibia, talus and mid-foot bones. Bone Spine 2008;75:341–4.
334 Letters to the editor / Joint Bone Spine 79 (2012) 323–334

Walter Alberto Sifuentes Giraldo a,∗ c Servicio de Radiología, Hospital Universitario

María Blázquez Cañamero a Ramón y Cajal, Ctra. Colmenar Viejo Km. 9,100,
Enrique Navas Elorza b 28034 Madrid, Spain
Ignacio Gallego Rivera c
∗ Corresponding author. Tel./Fax: +34 91 33 68 751.
Mónica Vázquez Díaz a
a Servicio de Reumatología, Hospital Universitario E-mail address: [email protected]
Ramón y Cajal, Ctra. Colmenar Viejo Km. 9,100, (W.A. Sifuentes Giraldo)
28034 Madrid, Spain
b Servicio de Enfermedades Infecciosas, Hospital
8 December 2011
Available online 26 January 2012
Universitario Ramón y Cajal, Ctra. Colmenar Viejo
doi:10.1016/j.jbspin.2011.12.002
Km. 9,100, 28034 Madrid, Spain

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