Short-term sequential therapy, DMab therapy after a short-term TPTD therapy, did not significantly change hip BMD and bone turnover marker in patients with severe osteoporotic hip fracture. However, it significantly improved spine BMD in both groups. This might be due to the difference in bone composition. Generally, BMD of the spine, which consists mostly cancellous bone, improved easilty after osteoporotic treatment. TPTD is well known for improving cancellous bone density and reducing cortical porosity [14, 15]. Therefore, the short term TPTD therapy was able to affect cancellous bone, whereas it was too short to reduce cortical porosity. In order to ensure fracture healing in patients with hip fracture, the process of bone formation should be adequately established in the early stages of fracture healing. Because the femur necks are composed mainly of cortical bones, the use of appropriate bone-forming agents is important for fracture healing. Therefore, previous studies reported sequential or combination treatment involving TPTD and denosumab therapies [13, 16, 17].
In the DATA-Switch study, TPTD was used for two years, with satisfactory results reported for the treatment of high-fracture risk groups following a switch to denosumab [18].
In the real world, however, compliance with TPTD therapy is difficult due to exorbitant cost [19, 20]. Although the results of this study were not statistically significant, we found that denosumab conversion after 3 months of TPTD use may be effective in patients with a high risk of fracture.
Almirol EA et al. [21] performed the randomized placebo-control study to evaluate the short-term effect (8 weeks) of TPTD in patients with lower-extremity stress fracture. Short-term TPTD treatment showed anabolic effects suggesting that TPTD may accelerate fracture healing in premenopausal women with lower-extremity stress fractures.
Kang et al. [22] performed a prospective comparative study to determine whether 3 months of TPTD therapy may be effective for preventing of fracture progression in patients with osteoporotic vertebral compression fractures (VCF) at the thoracolumbar spine. However, they found that 3-month treatment with TPTD did not prevent the progression of fractured vertebral body collapse or kyphotic changes in patients with osteoporosis. Similar with this study, sequential therapy was used, short-term TPTD followed by switch to denosumab for 1 year in our study. Spine BMD improved but the hip BMD did not show a statistically significant difference during the 1-year follow-up. In addition, both groups showed successful bone union at 1-year follow- up.
There are several limitations to this study. First, this was a retrospective study assessing a small sample of patients. Therefore, based on the results of this study, a well-planned RCT study is needed. Second, bone turnover markers were not measured between 3 and 6 months, and the level of validation for serum markers may differ between two hospitals. Further studies are needed to evaluate the BTM levels simultaneously at a central lab. In addition, a number of studies should be assessed by adding a reference interval for Koreans, and consensus on the timing of BTM measurement after fracture. Third, there was no objective assessment of the degree of bone union. In order to accurately assess the degree of bone union, all patients should be evaluated with imaging tests, including CT scan. Forth, baseline value of vitamin D was difference between two groups. However, that did not significantly affect the improvement of BMD because all patients were supplemented with calcium and vitamin D equally.