Interplay between low plasma RANKL and VDR-FokI polymorphism in lumbar disc herniation independently from age, body mass, and environmental factors: a case-control study in the Italian population.
OBJECTIVE
Aim of this study was to investigate RANKL and osteoprotegerin plasma concentrations in patients affected by disc herniation, the most common epiphenomenon of disc degenerative diseases, and in a matched cohort of healthy subjects and whether the expression of these markers was associated to a polymorphism of the vitamin D receptor gene.


METHODS
For this case-control study, 110 consecutive cases affected by lumbar disc herniation (confirmed by MRI) and 110 healthy age- and sex-matched controls were enrolled. Subjects affected by any other pathology were excluded. RANKL and osteoprotegerin were measured in plasma by immunoassays. The difference in these markers between cases and controls was assessed by t test. The correlation between osteoimmunological markers concentrations, anthropometrical variables, and the expression of the pathology was statistically assessed (Pearson's test) along with the association (Fisher's exact test) with the vitamin D receptor gene genotype, determined elsewhere.


RESULTS
Despite comparable osteoprotegerin concentrations, cases, altogether or grouped for gender, express lower RANKL and, consequently, RANKL-to-osteoprotegerin ratio. While in cases RANKL and osteoprotegerin concentrations were independent from age and BMI, in controls they increased with age. Disc herniation was strongly associated with RANKL and the presence of the F allele of the VDR gene.


CONCLUSIONS
Whether vertebral bone changes precede or follow cartilage deterioration in intervertebral disc degeneration is not known. Our results suggest a reduced bone turnover rate, associated to a specific genetic background, in patients affected by lumbar disc herniation which could be one of the favoring factors for disc degeneration.
Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italia.
Veronica
V
Sansoni
Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italia.
Silvia
S
Perego
Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italia.
Alessandra
A
Colombini
Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italia.|Vita-Salute San Raffaele University, Milan, Italia.
Giuseppe
G
Banfi
Scoliosis Unit, Department of Orthopedics and Traumatology-Spine Surgery III, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italia.
Marco
M
Brayda-Bruno
Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milan, Italia. giovanni.lombardi@grupposandonato.it.
Giovanni
http://orcid.org/0000-0002-8365-985X
G
Lombardi
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D004777:Environment; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007405:Intervertebral Disc Displacement / Q000097:blood / Q000209:etiology / Q000235:genetics*; D007558:Italy; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011110:Polymorphism, Genetic; D053245:RANK Ligand / Q000097:blood*; D018167:Receptors, Calcitriol / Q000235:genetics*; D012307:Risk Factors
D015415:Biomarkers; D005819:Genetic Markers; D053244:Osteoprotegerin; D053245:RANK Ligand; D018167:Receptors, Calcitriol; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human
Disc herniation; OPG; RANKL; VDR polymorphisms