Clinically Indicated Corticosteroids Do Not Affect Bone Turnover During Immune Restoration of Severely Lymphopenic HIV-Infected Patients.
Lymphopenia, corticosteroids, antiretroviral therapy (ART), and inflammation negatively impact bone turnover and decrease bone mineral density, but their combined effect has not been evaluated. We examined the association between corticosteroids on bone turnover markers in severely lymphopenic HIV-infected patients initiating ART. Levels of osteocalcin (bone formation marker) and C-terminal telopeptide (CTX; bone resorption marker) were measured at baseline, weeks 4, 12, and 48 of ART in individuals with severe lymphopenia and opportunistic infection (OI) who received (n=28) or did not receive corticosteroids (n=30) during the first year of ART, and in a control group with CD4 >200 (n=15). Wilcoxon tests were used to compare median values of variables between groups. Correlations between plasma interleukin (IL)-6 and tumor necrosis factor (TNF) levels with bone turnover marker levels were performed using Spearman's coefficient. Individuals given corticosteroids received a median of 21 days at a 35 mg prednisone-equivalent daily dose. Individuals with severe lymphopenia had lower osteocalcin levels at baseline and week 4 and higher CTX levels at ART initiation vs.


METHODS
Bone turnover markers did not differ in severely lymphopenic persons according to corticosteroid receipt. In those with severe lymphopenia, higher IL-6 was associated with higher CTX levels at ART initiation only. HIV-infected patients with severe lymphopenia and OI had lower levels of bone formation and higher levels of bone resorption than those initiating ART at higher CD4. Corticosteroid use, as prescribed during OI, was not associated with bone turnover. In contrast, higher markers of systemic inflammation prior to ART were associated with greater bone resorption.
1 Division of Infectious Diseases, Department of Medicine, Stanford University , Palo Alto, California.
Philip M
PM
Grant
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Virginia
V
Sheikh
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Rebecca
R
DerSimonian
3 Leidos Biomedical Research, Inc. , Frederick National Laboratory for Cancer Research, Frederick, Maryland.
Adam
A
Rupert
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Gregg
G
Roby
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Alice
A
Pau
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Michael C
MC
Sneller
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Sheryl-Vi
SV
Rico
4 Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University , Baltimore, Maryland.
Todd T
TT
Brown
2 National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland.
Irini
I
Sereti
D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D001842:Bone and Bones / Q000502:physiology*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D024042:Collagen Type I; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin