Bone mineral density and cytokine levels during interferon therapy in children with chronic hepatitis B: does interferon therapy prevent from osteoporosis?
BACKGROUND
Our aim was to determinate bone mineral density (BMD), levels of biochemical markers and cytokines in children with chronic hepatitis B treated with interferon (IFN)-alpha and to investigate effect of IFN-alpha therapy on these variables. To the best of our knowledge, this is first study carried out about BMD and cytokine levels in pediatric patients with chronic hepatitis B treated with IFN-alpha.


METHODS
BMD, levels of parathyroid hormone (PTH), osteocalcin, C-terminal cross-linking telopeptide of type I collagen (CTX), calcium, alkaline phosphates (ALP), cytokines as TNF-alpha, interleukin (IL)-1beta, IL-2r, IL-6, and IL-8 were studied in 54 children with chronic hepatitis B (4-15 years old) treated with interferon alone (n = 19) or in combination with lamivudine (n = 35) for six months and as controls in 50 age-matched healthy children.


RESULTS
There was no significant difference in respect to serum IL-1beta, TNF-alpha and osteocalcin levels while serum IL-2r (p = 0.002), IL-6 (p = 0.001), IL-8 (p = 0.013), PTH (p = 0.029), and CTX (p = 0.021) levels were higher in children with chronic hepatitis B than in healthy controls. BMD of femur neck (p = 0.012) and trochanter (p = 0.046) in patients were higher than in healthy controls. There was a statistically significant correlation between serum IL-1beta and osteocalcin (r = -0.355, p < 0.01); between serum IL-8 and CTX levels (r = 0.372, p = 0.01), and ALP (r = 0.361, p = 0.01); between serum ALP and femur neck BMD (r = 0.303, p = 0.05), and trochanter BMD (r = 0.365, p = 0.01); between spine BMD and IL-2R (r = -0.330, p < 0.05).


CONCLUSIONS
In conclusion, our study suggest that BMD of femur, serum IL-2r, IL-6, IL-8, PTH, and CTX levels were higher in children with chronic hepatitis B treated with IFN-alpha alone or combination with lamivudine than in healthy children. High femur BMD measurements found in patients may suggest that IFN-alpha therapy in children with chronic hepatitis B could contribute indirectly to prevent from hip osteoporosis. Additionally, further investigations on effects of IFN-alpha for bone structure in children should be performed in the future.
Gur
Ali
A
Department of Physical Medicine and Rehabilitation, Medical Faculty, Dicle University, Diyarbakir, Turkey. alig@dicle.edu.tr
Dikici
Bünyamin
B
Nas
Kemal
K
Bosnak
Mehmet
M
Haspolat
Kenan
K
Sarac
Aysegul Jale
AJ
D000293:Adolescent; D000998:Antiviral Agents / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D016207:Cytokines / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D005269:Femur / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007378:Interleukins / Q000097:blood; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D010024:Osteoporosis / Q000517:prevention & control*; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D015375:Receptors, Interleukin-2 / Q000097:blood; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
D000998:Antiviral Agents; D024042:Collagen Type I; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D010281:Parathyroid Hormone; D010455:Peptides; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; C052929:collagen type I trimeric cross-linked peptide; D019259:Lamivudine; D003094:Collagen