In this analysis, the rates of achieving BMD ≥ −2.5 SD as the T2T goal by TPTD and ANL treatment were evaluated. It was found that, in participants with L2-4 BMD < −2.5 SD at baseline, 13.6% achieved the target after 72 weeks of treatment with TPTD, and 20.5% achieved the target with a subsequent switch to ALN at 120 weeks. In the group that received ALN treatment for 120 weeks, 22.2%, 11.7%, and 7.3% of participants achieved the target L2-4, total hip, and femoral neck BMDs, respectively.

The achievement of T2T goals with TPTD has already been reported using the data from the TOWER trial [19]. The proportions achieving the goal BMDs were 21.9% for L2-4 BMD and 14.5% for femoral neck BMD at 72 weeks [19], higher than the current results. The differences may be explained by differences in the participants’ ages. The mean age of the participants was 74 years in the TOWER trial and 81 years in JOINT-05.

Compared by measurement site, the proportion achieving the T2T BMD goal was relatively low at the femoral neck site compared to the L2-4 and total hip sites. One reason for the difference was that the baseline T-score was lower at the femoral neck than at the other sites. If BMD was measured at more than one site, the site more likely to achieve the goal should be selected.

Recently, European experts convened a consensus conference and compiled a report on T2T goals for osteoporosis [20]. There was also consensus that a T2T strategy is applicable to osteoporosis, and that BMD is currently the most clinically appropriate target. With regard to the definition of a specific BMD treatment target and timeframes applicable to T2T, no clear consensus was reached; experts emphasized that these would need to be individually determined.

In the present analysis, about half of the participants had L2-4 BMD < −2.5 SD at baseline (46.3% in the TPTD-ALN group and 53.0% in the ALN group), and 20% of participants achieved BMD ≥ −2.5 SD after 120 weeks of treatment. According to the American Society of Bone and Metabolism and the United States National Osteoporosis Foundation (NOF), patients recommended to be offered drugs, such as bisphosphonate that have at least a 50% chance of achieving their goals within 3 to 5 years of starting treatment [12]. The remaining 80% of participants require further follow-up at least 3 years, and changes in treatment should be considered based on periodic BMD measurements. Moreover, another target should be set for participants with L2-4 BMD ≥ −2.5 SD at baseline.

In this analysis, the relationship between the BMD level and incident vertebral fractures was also confirmed. With TPTD treatment, the incidence of fractures was not necessarily dependent on BMD status. It may be due to the change of bone quality other than BMD. In fact, TPTD has been reported to increased material properties of bone [21]. Factors of bone quality other than changes in BMD that affect bone strength may also need to be taken into account in treatment.

This study had several limitations. The current study included data of participants in the JOINT-05 study, which included patients with osteoporosis and a high fracture risk. Because ALN is also used in osteoporotic patients with low fracture risk, the T2T goal achievement rate with ALN in particular may need to be re-evaluated in patients with a wider range of fracture risk. Not all 3 BMD sites were measured in all participants, and the number of participants for whom BMD was measured varied. The achievement rate in total hip BMD was higher in the TPTD-ALN group (23.1%) than in the ALN group (11.7%), but it was not statistically significant. Although this difference may be due to differences in therapeutic agents, it should be verified by studies with appropriate sample sizes. The background factors contributing to the difference between T2T and non-T2T achievers were unclear. More detailed studies may be needed that include information on patients' bone metabolic turnover and lifestyle habits. Incident vertebral fractures were evaluated in all participants, but BMD was not measured in all of them. Therefore, the relationship between BMD status and fracture incidence was not robust. However, the trends in incident fracture at the 3 measurement sites were identical, suggesting the generalizability of the results.

In conclusion, during the 1.5-year treatment period, more than 20% of participants with osteoporosis achieved BMD ≥ −2.5 SD as a T2T goal. Since the achievement level differed depending on the site of BMD measurement, the appropriate site should be selected according to the baseline BMD level of the patient.