Postmenopausal osteoporosis arises from imbalanced osteoclast and osteoblast activity, and mounting evidence suggests a role for the osteoimmune system in bone homeostasis. Bisphosphonate (BP) is an antiresorptive agent, but its treatment failure rate can be as high as 40%. Here, we performed single-cell RNA sequencing on peripheral immune cells from carefully selected postmenopausal women: non-osteoporotic, osteoporosis improved after BP treatment, and BP-failed cases. We found an increase in myeloid cells in patients with osteoporosis (specifically, T cell receptor+ macrophages). Furthermore, lymphoid lineage cells varied significantly, notably elevated natural killer cells (NKs) in the BP-failed group. Moreover, we provide fruitful lists of biomarkers within the immune cells that exhibit condition-dependent differences. The existence of osteoporotic- and BP-failure-specific cellular information flows was revealed by cell–cell interaction analysis. These findings deepen our insight of the osteoporosis pathology enhancing comprehension of the role of immune heterogeneity in postmenopausal osteoporosis and BP treatment failure.

Degenerative lumbar spinal disease (DLSD), including spondylolisthesis and spinal stenosis, is increasing due to the aging population. Along with the disease severity, lumbar interbody fusion (LIF) is a mainstay of surgical treatment through decompression, the restoration of intervertebral heights, and the stabilization of motion segments. Currently, pseudoarthrosis after LIF is an important and unsolved issue, which is closely related to osteobiologies. Of the many signaling pathways, the bone morphogenetic protein (BMP) signaling pathway contributes to osteoblast differentiation, which is generally regulated by SMAD proteins as common in the TGF-β superfamily. BMP-2 and -4 are also inter-connected with Wnt/β-catenin, Notch, and FGF signaling pathways. With the potent potential for osteoinduction in BMP-2 and -4, the combination of allogenous bone and recombinant human BMPs (rhBMPs) is currently an ideal fusion material, which has equalized or improved fusion rates compared to traditional materials. However, safety issues in the dosage of BMP remain, so overcoming current limitations will provide significant advancement in spine surgery. In the future, translational research and the application of clinical study will be important to overcome the current limitations of spinal surgery.

(1) Background: Bisphosphonate treatment failure is one of the most difficult clinical problems for patients with osteoporosis. This study aimed to analyze the incidence of bisphosphonate treatment failure, associated radiological factors, and effect of fracture healing in postmenopausal women with osteoporotic vertebral fractures (OVFs). (2) Methods: A total of 300 postmenopausal patients with OVFs who were prescribed bisphosphonate were retrospectively analyzed and divided into two groups according to the treatment response: response (n = 116) and non-response (n = 184) groups. The radiological factors and the morphological patterns of OVFs were included in this study. (3) Results: The initial BMD values of the spine and femur in the non-response group were significantly lower than those in the response group (all Ps < 0.001). The initial BMD value of the spine (odd ratio = 1.962) and the fracture risk assessment tool (FRAX) hip (odd ratio = 1.32) showed statistical significance in logistic regression analysis, respectively (all Ps < 0.001). (4) Conclusions: The bisphosphonate non-responder group showed a greater decrease in BMD over time than the responder group. The initial BMD value of the spine and the FRAX hip could be considered radiological factors influencing bisphosphonate non-response in the postmenopausal patients with OVFs. The failure of bisphosphonate treatment for osteoporosis has a possible negative on the fracture healing process in OVFs.