Publications

G-protein-coupled receptors (GPCRs) are key regulators of skeletal homeostasis and are likely important in fracture healing. Because GPCRs can activate multiple signaling pathways simultaneously, we used targeted disruption of G(i) -GPCR or activation of G(s) -GPCR pathways to test how each pathway functions in the skeleton. We previously demonstrated that blockade of G(i) signaling by pertussis toxin (PTX) transgene expression in maturing osteoblastic cells enhanced cortical and trabecular bone formation and prevented age-related bone loss in female mice. In addition, activation of G(s) signaling by expressing the G(s) -coupled engineered receptor Rs1 in maturing osteoblastic cells induced massive trabecular bone formation but cortical bone loss. Here, we test our hypothesis that the G(i) and G(s) pathways also have distinct functions in fracture repair. We applied closed, nonstabilized tibial fractures to mice in which endogenous G(i) signaling was inhibited by PTX, or to mice with activated G(s) signaling mediated by Rs1. Blockade of endogenous G(i) resulted in a smaller callus but increased bone formation in both young and old mice. PTX treatment decreased expression of Dkk1 and increased Lef1 mRNAs during fracture healing, suggesting a role for endogenous G(i) signaling in maintaining Dkk1 expression and suppressing Wnt signaling. In contrast, adult mice with activated Gs signaling showed a slight increase in the initial callus size with increased callus bone formation. These results show that G(i) blockade and G(s) activation of the same osteoblastic lineage cell can induce different biological responses during fracture healing. Our findings also show that manipulating the GPCR/cAMP signaling pathway by selective timing of G(s) and G(i) -GPCR activation may be important for optimizing fracture repair.

OBJECTIVE

The objective was to determine individual and dyadic factors associated with effective contraceptive use among human immunodeficiency virus (HIV)-infected women accessing antiretroviral therapy (ART) in rural Uganda.

STUDY DESIGN

HIV-infected women enrolled in the Uganda AIDS Rural Treatment Outcomes cohort completed questionnaires (detailing sociobehavioral characteristics, sexual and reproductive history, contraceptive use, fertility desires) and phlebotomy (October 2011-March 2013). We describe prevalence of effective contraceptive use (i.e., consistent condom use and/or oral contraceptives, injectable hormonal contraception, intrauterine device, female sterilization) in the previous 6 months among sexually active, nonpregnant women (18-40 years). We assessed covariates of contraceptive use using multivariable logistic regression.

RESULTS

A total of 362 women (median values: age 30 years, CD4 count 397 cells/mm(3), 4.0 years since ART initiation) were included. Among 284 sexually active women, 50% did not desire a(nother) child, and 51% had a seroconcordant partner. Forty-five percent (n=127) reported effective contraceptive use, of whom 57% (n=72) used condoms, 42% (n=53) injectables, 12% (n=15) oral contraceptives and 11% (n=14) other effective methods. Dual contraception was reported by 6% (n=8). Only "partnership fertility desire" was independently associated with contraceptive use; women who reported that neither partner desired a child had significantly increased odds of contraceptive use (adjusted odds ratio: 2.40, 95% confidence interval: 1.07-5.35) compared with women in partnerships where at least one partner desired a child.

CONCLUSIONS

Less than half of sexually active HIV-infected women accessing ART used effective contraception, of which 44% (n=56) relied exclusively on male condoms, highlighting a continued need to expand access to a wider range of longer-acting female-controlled contraceptive methods. Association with partnership fertility desire underscores the need to include men in reproductive health programming.

IMPLICATIONS STATEMENT

Less than half of sexually active HIV-infected women accessing ART in rural Uganda reported using effective contraception, of whom 44% relied exclusively on the male condom. These findings highlight the need to expand access to a wider range of longer-acting, female-controlled contraceptive methods for women seeking to limit or space pregnancies. Use of contraception was more likely when both the male and female partner expressed concordant desires to limit future fertility, emphasizing the importance of engaging men in reproductive health programming.