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Abstract
Purpose
The aromatase inhibitors cause bone loss by estrogen depletion. Zoledronic acid (ZA) can prevent bone mineral density (BMD) loss associated with the use of aromatase inhibitors. Accordingly interest has arisen in measuring surrogate markers of bone resorption to monitor the response of treatment of BMD loss in place of a radiologic assessment. This study was designed to determine whether ZA would prevent bone loss that is known to occur with letrozole and identified surrogate markers of bone resorption in an animal model.
Methods
In ovariectomized or sham-operated rat, we administrated ZA and letrozole to 5 different groups including: a sham operation control group (OC), a group in which an ovariectomy was performed followed by saline administration (OS), an ovariectomy with ZA treatment group (OZ), an ovariectomy with letrozole treatment group (OL) and an ovariectomy with ZA and letrozole combined treatment group (OZL). The levels of serum osteocalcin, serum bone alkaline phosphatase (BALP), serum calcium and urine N-telopeptide (NTX) and BMD were estimated and compared at the same periods for each group. The distinct microscopic findings of proximal tibia at week sixteen were also compared.
Results
Significantly reduced levels of urine NTX and significantly increased BMD were measured in the OZ group. In the OL group no difference was seen in in BMD in comparison to the OS group. However, a significant increase in BMD was measured in the OZL group. Urine NTX levels were measured and found to be lower in the OL group and significantly lower in the OZL group. Serum osteocalcin levels were similar to each other for each group. Levels of serum calcium and BALP were significantly lower in the OZL group than in the OS group.
Figures and Tables
Fig 1
The changes of body weight in each group at the same periods. This graph shows change of body weight before operation, 8 weeks and 16 weeks after operation. In each group the body weight is increase significantly at 16 weeks after ovariectomy (p<0.05).
Fig 2
The changes of bone mineral density, femur in each group at the same periods: before operation, 8 weeks and 16 weeks after operation.
Fig 3
The changes of the concentration of serum biochemical markers, such as osteocalcin (A), serum calcium (B), urine calcium (C), BALP (D) in each group at the same periods: before operation, 8 weeks and 16 weeks after operation.
Fig 4
The changes of the concentration of urine biochemical marker, NTX in each group at the same periods: before operation, 8 weeks and 16 weeks after operation.
Fig 5
The distinct pathologic findings of proximal tibia in each group: OC (A), OS (B), OZ (C), OL (D) and OZL (E) at 16 weeks after operation (H&E stain, ×100). The distinct histologic findings of proximal tibia in each group at 16 weeks after operation. OC (A) and OS (B): control and saline infusion group show silmilar thickness of bony trabeculae. OZ (C): Zoledronic acid infusion group reveals thikended bony trabeculae compared to OC and OS. OL (D): Letrozole group shows thining of bony trabeculae. Some trabeculae reveals thinned and tappered ends (left lower corner). OZL (E): Both Letrozole and Zodedronic acid infusion group reveal markedly thickened bony trabeculae (H&E stain, ×100).
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