Jens Bay Vegger

PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats

PTH and strontium ranelate (SrR) have both been shown to reduce bone loss induced by immobilization. PTH is a potent bone anabolic agent, whereas SrR has been suggested to be an antiresorptive as well as a bone anabolic agent. The aim of the study was to investigate whether PTH, SrR, and PTH and SrR in combination could counteract immobilization-induced bone loss in a rat model. Immobilization was induced by injecting 4IU Botox (BTX) into the muscles of the right hind limb. Seventy-two female Wistar rats, 3-months-old, were divided into the following groups: Baseline, Controls, BTX, BTX+PTH, BTX+SrR, and BTX+PTH+SrR (n=12 in each group). PTH was given as injections (SC) at a dosage of 60μg/kg/d, and SrR as 900mg/kg/d in the diet. The experiment lasted for 4weeks. BTX resulted in lower trabecular bone formation rate (-68%) and periosteal bone formation rate (-91%), and a higher fraction of osteoclast-covered surfaces (+53%) compared with controls. This was accompanied by significantly lower trabecular bone volume fraction (-24%), trabecular thickness (-16%), and bone strength (-14% to -32% depending on site). PTH alone counteracted immobilization-induced losses in trabecular (4-fold increase vs. BTX) and periosteal (5-fold increase vs. BTX) bone formation rate, trabecular thickness (+25% vs. BTX) and femoral neck strength (+24% vs. BTX). In contrast, SrR did not influence BTX-induced loss of bone formation rate, trabecular bone volume fraction, trabecular thickness, or bone strength. Finally, no additive effect was found when PTH and SrR treatments were combined. In conclusion, PTH counteracted loss in bone architecture and bone strength in immobilized rats, whereas as no effect of SrR was found. Moreover, no additional effect was found by combining PTH with SrR.

Additive effect of PTH (1–34) and zoledronate in the prevention of disuse osteopenia in rats

Immobilization is known to cause a rapid bone loss due to increased osteoclastic bone resorption and decreased osteoblastic bone formation. Zoledronate (Zln) is a potent anti-resorptive pharmaceutical, while intermittent PTH is a potent bone anabolic agent. The aim of the present study was to investigate whether PTH or Zln alone or in combination could prevent immobilization-induced osteopenia. Immobilization was achieved by injecting 4IU Botox (BTX) into the right hind limb musculature. Seventy-two 16-week-old female Wistar rats were randomized into 6 groups; baseline (Base), control (Ctrl), BTX, BTX+PTH, BTX+Zln, and BTX+PTH+Zln. PTH (1-34) (80μg/kg) was given 5days/week and Zln (100μg/kg) was given once at study start. The animals were killed after 4weeks of treatment. The bone properties were evaluated using DEXA, μCT, dynamic bone histomorphometry, and mechanical testing. BTX resulted in lower femoral trabecular bone volume fraction (BV/TV) (-25%, p<0.05), lower tibial trabecular bone formation rate (BFR/BS) (-29%, p<0.05), and lower bone strength (Fmax) at the distal femur (-19%, p<0.001) compared with Ctrl. BTX+PTH resulted in higher femoral BV/TV (+31%, p<0.05), higher tibial trabecular BFR/BS (+297%, p<0.05), and higher Fmax at the distal femur (+11%, p<0.05) compared with BTX. BTX+Zln resulted in higher femoral BV/TV (+36%, p<0.05), lower tibial trabecular BFR/BS (-93%, p<0.05), and higher Fmax at the distal femur (+10%, p<0.05) compared with BTX. BTX+PTH+Zln resulted in higher femoral BV/TV (+70%, p<0.001), higher tibial trabecular BFR/BS (+59%, p<0.05), and higher Fmax at the distal femur (+32%, p<0.001) compared with BTX. In conclusion, BTX-induced immobilization led to lower BV/TV, BFR/BS, and Fmax. In general, PTH or Zln alone prevented the BTX-induced osteopenia, whereas PTH and Zln given in combination not only prevented, but also increased BV/TV and BFR/BS, and maintained Fmax at the distal femoral metaphysis compared with Ctrl.

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss.