LARC Implant Use Does Not Exacerbate Bone Loss Associated With Hindlimb Unloading

Abstract

Combined oral contraceptives (COC; ethinyl estradiol and progestin) reduce exercise-induced gains in bone mineral density (BMD), possibly by suppressing bone turnover. Long-acting reversible contraceptives (LARC; progestin-only) provide many practical advantages over COC and will likely be recommended for female astronauts on long-duration missions; however, the impact on bone health with unloading is unknown. PURPOSE: To determine if LARC use will blunt loss of bone associated with hindlimb unloading (HU) METHODS: Virgin female Sprague-Dawley rats (n=52; 4-mo-old) were singly housed and randomly assigned to placebo (PL) and LARC groups, via an implanted slow-release etonogestrel pellet (0.00ug/d vs. 0.30ug/d). A week later, animals were further randomized to weight bearing (WB) and HU groups (n=13/subgroup) for 6 weeks. Calcein injections were delivered 9 and 2 days prior to termination. Pre/post-HU, proximal tibia metaphysis (PTM) and the tibia mid-diaphysis (TD) were scanned with in vivo peripheral quantitative computed tomography. At termination tibiae were stored for mechanical testing and dynamic/static histomorphometry. Univariate and repeated measures 2-way ANOVA were used. RESULTS: Despite increasing their food intake during HU (p<0.01), HU animals lost weight and weighed less than WB animals starting on HU week 2 (p<0.01). Irrespective of pellet type, HU resulted in a loss of total and cancellous volumetric BMD (vBMD) at the PTM (p<0.01), reduced cortical thickness at the PTM and TD p<0.01), and reduced endosteal and periosteal mineralization (MS/BS, MAR, and BFR; p<0.02) at the TD compared to WB animals. Irrespective of loading group, at the PTM LARC animals lost cancellous vBMD (p<0.05), but had an increase in osteoid (organic bone matrix; p<0.04) compared to PL animals. PTM BV/TV and Tb.Th were greater in PL-WB animals compared to PL-HU animals only (p<0.04). Similarly, ultimate force was greater in PL-WB animals compared to PL-HU animals only (p<0.02). CONCLUSIONS: On balance, LARC implantation did not blunt nor worsen the bone response to unloading. LARC appear to be a viable option for premenopausal female astronauts selected for long-duration missions. This work is supported by the Translational Research Institute for Space Health through Cooperative Agreement NNX16AO69A