Asia-Pacific consensus on long-term and sequential therapy for osteoporosis.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Relationship between Serum 25-hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults with Osteoporosis/Fractures.

OBJECTIVE: To evaluate the association of serum 25-hydroxyvitamin D (25(OH)D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. METHODS: This multicenter cross-sectional study recruited menopausal females and males ≥ 50 years old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. RESULTS: 3,003 individuals were stratified by 25(OH)D levels: 720 individuals (24%) < 20 ng/mL, 1,338 individuals (44.5%) 20-29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In un-adjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH)D levels were inversely associated with FRAX (Fracture Risk Assessment Tool) scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D ≧20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. CONCLUSION: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by FRAX. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

The no-observed-adverse-effect level of phthalates promotes proliferation and cell cycle progression in normal human breast cells.

OBJECTIVE: The data on the association between phthalates and breast cancer risk remains inconsistent. This study aimed to explore the possible mechanism of low-dose exposures of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP), on breast tumorigenesis. METHODS AND METHODS: MCF-10A normal breast cells were treated with phthalates (10 and 100 nM) and 17ß-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue. Cell viability, cycle, and apoptosis were detected by MTT assay, flow cytometry, and TUNEL assay respectively. The expression levels of related proteins were determined by Western blot. RESULTS: Like E2, both 10 nM and 100 nM phthalates exerted significantly higher cell viability, lower apoptosis, and increased cell numbers in the S and G2/M phases with up-regulation of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1, compared with the control group. Significant increase in PDK1, P13K, p-AKT, p-mTOR, and BCL-2 expression and a decrease in Bax protein, cytochrome C, caspase 8, and caspase 3 levels were noted in cells treated with 10 nM and 100 nM phthalates and E2, compared with the control group and MCF-10A cells co-cultured with fibroblasts. The effects of the three phthalates were noted to be dose-dependent. CONCLUSIONS: The results indicate that phthalates at a level below its no-observed-adverse-effect concentration, as defined by the current standards, still induce cell cycle progression and proliferation as well as inhibit apoptosis of normal breast cells. Thus, the possibility of breast tumorigenesis through chronic phthalate exposure should be considered.

Regulation of the cell cycle and P13K/AKT/mTOR signaling pathway by phthalates in normal human breast cells.

OBJECTIVE: To investigate the impact of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), in breast carcinogenesis. MATERIALS AND METHODS: MCF-10A normal breast cells were treated with phthalates (100 nM) and 17ß-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue adjacent to estrogen receptor positive primary breast cancers. Cell viability was determined using a 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell cycles were analyzed using flow cytometry. The proteins involving cell cycles and P13K/AKT/mTOR signaling pathway were then evaluated by Western blot analysis. RESULTS: MCF-10A co-cultured cells treated with E2, BBP, DBP, and DEHP exhibited a significant increase in cell viability using MTT assay. The expressions of P13K, p-AKT, and p-mTOR, as well as PDK1 expression, were significantly higher in MCF-10A cells treated with E2 and phthalates. E2, BBP, DBP, and DEHP significantly increased cell percentages in the S and G2/M phases. The significantly higher expression of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1 in MCF-10A co-cultured cells were induced by E2 and these three phthalates. CONCLUSION: These results provide consistent data regarding the potential role of phthalates exposure in the stimulating proliferation of normal breast cells, enhancing cell viability, and driving P13K/AKT/mTOR signaling pathway and cell cycle progression. These findings strongly support the hypothesis that phthalates may play a crucial role in breast tumorigenesis.

High Content of Thermoplastic Starch, Poly(butylenes adipate-co-terephthalate) and Poly(butylene succinate) Ternary Blends with a Good Balance in Strength and Toughness.

The ternary blends of a high content of thermoplastic starch (TPS), poly(butylenes adipate-co-terephthalate) (PBAT), and poly(butylene succinate) (PBS) were first melt-compounded in a twin screw extruder. The TPS contents in ternary blends were fixed at 60 wt%. The miscibility, morphology, thermal behavior, mechanical properties, and thermal resistance of the blends were investigated. The results showed that dispersions of PBS and PBAT minor phases improved the tensile strength and elongation at break. TPS/PBS/PBAT60/10/30 formed a good balance in strength and toughness. Dynamic mechanical analysis of the blends exhibits an intermediate and peak suggesting the ternary blend is compatible. Minor phase-separated structure SEM results showed that TPS/PBS/PBAT60/10/30 blend formed a typical mixture with core-shell morphology. As the PBAT composition was increased, phase morphology changes occurred in the blends, leading to decreased values of complex viscosity, storage modulus, and loss modulus. Moreover, the thermal resistances and melt flow properties of the materials were also studied by analysis of the heat deflection temperature (HDT) and melt flow index (MFI) value in the work.

Asia-pacific consensus on osteoporotic fracture prevention in postmenopausal women with low bone mass or osteoporosis but no fragility fractures.

Postmenopausal women are at significant risk for osteoporotic fractures due to their rapid bone loss. Half of all postmenopausal women will get an osteoporosis-related fracture over their lifetime, with 25% developing a spine deformity and 15% developing a hip fracture. By 2050, more than half of all osteoporotic fractures will occur in Asia, with postmenopausal women being the most susceptible. Early management can halt or even reverse the progression of osteoporosis. Consequently, on October 31, 2020, the Taiwanese Osteoporosis Association hosted the Asia-Pacific (AP) Postmenopausal Osteoporotic Fracture Prevention (POFP) consensus meeting, which was supported by the Asian Federation of Osteoporosis Societies (AFOS) and the Asia Pacific Osteoporosis Foundation (APOF). International and domestic experts developed ten applicable statements for the prevention of osteoporotic fractures in postmenopausal women with low bone mass or osteoporosis but no fragility fractures in the AP region. The experts advocated, for example, that postmenopausal women with a high fracture risk be reimbursed for pharmaceutical therapy to prevent osteoporotic fractures. More clinical experience and data are required to modify intervention tactics.

Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: 2022 update.

Osteoporosis greatly increases the risk of fractures. Osteoporotic fractures negatively impact quality of life, increase the burden of care, and increase mortality. Taiwan is an area with a high prevalence of osteoporosis. This updated summary of guidelines has been developed by experts of the Taiwan Osteoporosis Association with the intention of reducing the risks of osteoporotic fractures and improving the quality of care for patients with osteoporosis. The updated guidelines compile the latest evidence to provide clinicians and other healthcare professionals with practical recommendations for the prevention, diagnosis, and management of osteoporosis under clinical settings in Taiwan.

A self-gelling starch-based sponge for hemostasis.

Uncontrolled bleeding remains one of the direct causes of high mortality. There is an urgent need for developing emergency hemostats capable of coping with uncontrolled bleeding. The commercial starch-based hemostatic powder (PerClot®) requires compression during application, which limits its application in hemostasis of irregular and non-compressed wounds. Herein, a boronic acid-modified thiol starch sponge (St-SP sponge) with self-gelling properties was developed for hemorrhage control. The results show that the St-SP sponge could quickly absorb blood, self-gel and self-heal to seal the bleeding sites. In addition, the St-SP sponge can rapidly initiate the coagulation cascade and promote the adhesion and aggregation of erythrocytes and platelets. The St-SP sponge exhibited significantly improved in vitro and in vivo hemostatic abilities as compared with PerClot. Notably, the St-SP sponge attained complete hemostasis without any compression in 61.5 s and made a great difference compared to PerClot (169 s) for the irregular wound constructed on the rabbit liver. In addition, the St-SP sponge had good hemocompatibility and cytocompatibility. It turns out that the newly developed St-SP sponge is a promising material for first-aid hemostasis of irregular and non-compressed wounds.

Starch-based shape memory sponge for rapid hemostasis in penetrating wounds.

Death caused by excessive blood loss has always been a global concern. Timely control of bleeding in incompressible penetrated wounds remains a great challenge. Here, we developed a shape memory sponge (SQG) based on modified starch and gelatin (Gel) to control the hemorrhage of penetrating wounds. The porous structure of SQG greatly enhanced the absorption of blood, and the adhesion of erythrocytes and platelets. The water absorption rate of SQG reached 1178.72 ± 12.18% in 10 s. SQG quickly recovered its shape in water (∼3 s) and exhibited high mechanical strength (∼38 kPa), acting as a physically packed barrier to facilitate hemostasis. Furthermore, the positively charged sponges were conducive to activating platelets and promoting the release of coagulation factors. SQG sponges possessed the lowest blood coagulation index (BCI) of 21.32 ± 0.19%, and presented good biocompatibility and obvious inhibitory effect on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Moreover, SQG sponges controlled complete bleeding in 69 ± 20 s and a bleeding loss of 334 ± 138 mg was observed, nearly 50% lower than that of gelatin sponge in rabbit liver penetrating wounds. Overall, SQG possesses a combination of potent shape recovery, rapid hemostasis, and excellent antibacterial and degradation ability, enabling promising applications for hemostasis in non-compressible penetrating wounds.

Glutaraldehyde Crosslinked High Content of Amylose/Polyvinyl Alcohol Blend Films with Potent Tensile Strength and Young's Modulus.

In recent years, with the development of green environmental protection, starch film has become of interest due to the wide availability of sources, low price, and biodegradability. Amylose/polyvinyl alcohol (PVA) blend films crosslinked with different amounts of glutaraldehyde (GLU) were prepared by a solution casting method. The cross-linking degree, water sorption, tensile property, crystallization and section morphology of the films were examined. With the increase in glutaraldehyde concentration, the cross-linking degree of the blend film was improved. The wide-angle X-ray scattering (WAXS) result indicated that cross-linking hindered the crystallization of film. The section morphology of films was examined by scanning electron microscope (SEM). The results showed that the cross-linking degree of amylose film improved while the crystallinity decreased with the increase in glutaraldehyde content. Cross-linking had no obvious effect on the water sorption property of the blend films. The cross-linking modification significantly enhanced the tensile strength and Young's modulus, while it reduced the elongation at break of the blend films. It was found that the film with 0.5 wt % glutaraldehyde possessed the best performance: the tensile strength increased by 115%, while the elongation at break decreased by 18% even at high relative humidity (RH) of 90% compared to non-crosslinked films. The developed amylose/PVA blend films have promising application prospects as agricultural mulch films and packaging materials.

Enhanced Cell Osteogenesis and Osteoimmunology Regulated by Piezoelectric Biomaterials with Controllable Surface Potential and Charges.

Bone regeneration is a well-orchestrated process involving electrical, biochemical, and mechanical multiple physiological cues. Electrical signals play a vital role in the process of bone repair. The endogenous potential will spontaneously form on defect sites, guide the cell behaviors, and mediate bone healing when the bone fracture occurs. However, the mechanism on how the surface charges of implant potentially guides osteogenesis and osteoimmunology has not been clearly revealed yet. In this study, piezoelectric BaTiO3/ß-TCP (BTCP) ceramics are prepared by two-step sintering, and different surface charges are established by polarization. In addition, the cell osteogenesis and osteoimmunology of BMSCs and RAW264.7 on different surface charges were explored. The results showed that the piezoelectric constant d33 of BTCP was controllable by adjusting the sintering temperature and rate. The polarized BTCP with a negative surface charge (BTCP-) promoted protein adsorption and BMSC extracellular Ca2+ influx. The attachment, spreading, migration, and osteogenic differentiation of BMSCs were enhanced on BTCP-. Additionally, the polarized BTCP ceramics with a positive surface charge (BTCP+) significantly inhibited M1 polarization of macrophages, affecting the expression of the M1 marker in macrophages and changing secretion of proinflammatory cytokines. It in turn enhanced osteogenic differentiation of BMSCs, suggesting that positive surface charges could modulate the bone immunoregulatory properties and shift the immune microenvironment to one that favored osteogenesis. The result provides an alternative method of synergistically modulating cellular immunity and the osteogenesis function and enhancing the bone regeneration by fabricating piezoelectric biomaterials with electrical signals.

Efficacy, safety and bioequivalence of the human-derived B-domain-deleted recombinant factor VIII TQG202 for prophylaxis in severe haemophilia A patients.

INTRODUCTION: Current treatment of severe haemophilia A includes prophylaxis with factor VIII (FVIII) replacement. The supply of plasma-derived FVIII is short in China. PURPOSE: To evaluate the efficacy and safety of a new B-domain deleted (BDD) recombinant FVIII (TQG202) produced by human-derived cells for prophylaxis in severe haemophilia A patients and compare the bioequivalence with Xyntha. METHODS: This multicentre, clinical trial consisted of an open-label, randomized, two-period cross-over trial assessing single-dose pharmacokinetics (PK), and a single-arm clinical trial evaluating the efficacy and safety of 24 weeks of TQG202 prophylaxis, and repeated PK were assessed after prophylaxis phase. The single-dose was 50 IU/kg in PK assessment, and the initial dose was 30 ± 5 IU/kg for prophylaxis. The primary endpoints of prophylaxis were the annualized bleeding rate (ABR) and the incremental recovery rate of the first administration. Adverse events (AEs) were recorded. RESULTS: Twenty-six participants were enrolled in the PK assessment and 81 participants in the prophylaxis phase. Mean age was 25.9 ± 10.8 years and all participants were male. The results of PK assessment showed TQG202 is bioequivalent to Xyntha. The total ABR was 2.0 (95% CI: 1.2-2.9) in prophylaxis phase. The mean incremental recovery rate of the first administration was .027 (95% CI: .026-.028) (IU/ml)/(IU/kg). AEs occurred in 42 participants, with an incidence of 51.9%. One severe AE not related to TQG202 occurred. No participants developed FVIII inhibitors. CONCLUSION: TQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice.

CRISPR-Cas9-mediated gene editing of the BCL11A enhancer for pediatric ß0/ß0 transfusion-dependent ß-thalassemia.

Gene editing to disrupt the GATA1-binding site at the +58 BCL11A erythroid enhancer could induce γ-globin expression, which is a promising therapeutic strategy to alleviate ß-hemoglobinopathy caused by HBB gene mutation. In the present study, we report the preliminary results of an ongoing phase 1/2 trial (NCT04211480) evaluating safety and efficacy of gene editing therapy in children with blood transfusion-dependent ß-thalassemia (TDT). We transplanted BCL11A enhancer-edited, autologous, hematopoietic stem and progenitor cells into two children, one carrying the ß0/ß0 genotype, classified as the most severe type of TDT. Primary endpoints included engraftment, overall survival and incidence of adverse events (AEs). Both patients were clinically well with multilineage engraftment, and all AEs to date were considered unrelated to gene editing and resolved after treatment. Secondary endpoints included achieving transfusion independence, editing rate in bone marrow cells and change in hemoglobin (Hb) concentration. Both patients achieved transfusion independence for >18 months after treatment, and their Hb increased from 8.2 and 10.8 g dl-1 at screening to 15.0 and 14.0 g dl-1 at the last visit, respectively, with 85.46% and 89.48% editing persistence in bone marrow cells. Exploratory analysis of single-cell transcriptome and indel patterns in edited peripheral blood mononuclear cells showed no notable side effects of the therapy.

Impaired interferon-γ signaling promotes the development of silicosis.

Silicosis is caused by inhalation of crystalline silica dust particles and known as one of the most serious occupational diseases worldwide. However, little is known about intrinsic factors leading to disease susceptibility. Single-cell sequencing of bronchoalveolar lavage fluid cells of mine workers with silicosis and their co-workers who did not develop silicosis revealed that the impaired interferon (IFN)-γ signaling in myeloid cells was strongly associated with the occurrence of silicosis. Global or myeloid cell-specific deletion of interferon γ receptor (IFN-γR) markedly enhanced the crystalline silica-induced pulmonary injury in wild-type but not in NLRP3 deficient mice. In vitro, IFN-γ priming of macrophages suppressed the crystalline silica-induced NLRP3 inflammasome activation partly by inducing the formation of spacious phagosomes with relatively reduced ratio of crystalline silica/phagosomal areas volumes to resistant crystalline silica-induced lysosomal membrane damage. Thus, these findings provide molecular insights into the intricate mechanisms underlying innate immunity-mediated host responses to environmental irritants.

CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation.

Osteolytic bone disease is a hallmark of multiple myeloma (MM). A significant fraction (~20%) of MM patients do not develop osteolytic lesions (OLs). The molecular basis for the absence of bone disease in MM is not understood. We combined PET-CT and gene expression profiling (GEP) of purified BM CD138+ MM cells from 512 newly diagnosed MM patients to reveal that elevated expression of cystatin M/E (CST6) was significantly associated with the absence of OL in MM. An enzyme-linked immunosorbent assay revealed a strong correlation between CST6 levels in BM serum/plasma and CST6 mRNA expression. Both recombinant CST6 protein and BM serum from patients with high CST6 significantly inhibited the activity of the osteoclast-specific protease cathepsin K and blocked osteoclast differentiation and function. Recombinant CST6 inhibited bone destruction in ex vivo and in vivo myeloma models. Single-cell RNA-Seq showed that CST6 attenuates polarization of monocytes to osteoclast precursors. Furthermore, CST6 protein blocks osteoclast differentiation by suppressing cathepsin-mediated cleavage of NF-κB/p100 and TRAF3 following RANKL stimulation. Secretion by MM cells of CST6, an inhibitor of osteoclast differentiation and function, suppresses osteolytic bone disease in MM and probably other diseases associated with osteoclast-mediated bone loss.

HRS phosphorylation drives immunosuppressive exosome secretion and restricts CD8+ T-cell infiltration into tumors.

The lack of tumor infiltration by CD8+ T cells is associated with poor patient response to anti-PD-1 therapy. Understanding how tumor infiltration is regulated is key to improving treatment efficacy. Here, we report that phosphorylation of HRS, a pivotal component of the ESCRT complex involved in exosome biogenesis, restricts tumor infiltration of cytolytic CD8+ T cells. Following ERK-mediated phosphorylation, HRS interacts with and mediates the selective loading of PD-L1 to exosomes, which inhibits the migration of CD8+ T cells into tumors. In tissue samples from patients with melanoma, CD8+ T cells are excluded from the regions where tumor cells contain high levels of phosphorylated HRS. In murine tumor models, overexpression of phosphorylated HRS increases resistance to anti-PD-1 treatment, whereas inhibition of HRS phosphorylation enhances treatment efficacy. Our study reveals a mechanism by which phosphorylation of HRS in tumor cells regulates anti-tumor immunity by inducing PD-L1+ immunosuppressive exosomes, and suggests HRS phosphorylation blockade as a potential strategy to improve the efficacy of cancer immunotherapy.

The Effectiveness of a Group Kickboxing Training Program on Sarcopenia and Osteoporosis Parameters in Community-Dwelling Adults Aged 50-85 Years.

Background: Sarcopenia and osteoporosis are important health issues faced by older people. These are often associated with each other and share common risk factors and pathologic mechanisms. In the recently revised consensus of the European Working Group on Sarcopenia in Older People, low muscle strength has been defined as the first characteristic of sarcopenia rather than a loss in muscle mass, and walking speed has been stated as an indicator of the severity of sarcopenia. It is believed that these markers of muscle function can be potentially reversed via exercise-based interventions. The purpose of this study was to evaluate the effects of kickboxing exercise training on the parameters of sarcopenia and osteoporosis in community-dwelling adults. Methods: In total, one hundred eligible subjects were randomized into an intervention group (n = 50) with 76% women and control group (n = 50) with 86% women. Both the intervention and control groups were provided with classroom lectures and personal consultations pertaining to sarcopenia and osteoporosis, whereas a 12-week kickboxing exercise training was arranged only for the intervention group. All anthropometric, physical performance, body composition, and bone mineral density measurements along with participant completed questionnaires were conducted before and after the training period. Results: After 12 weeks, 41 participants in the intervention group and 34 participants in the control group completed the final assessments. There was no difference between the intervention and control groups in terms of basic demographic data. The BMI (+1.14%) of the control group increased significantly during the study period. The waist circumference (-6.54%), waist-to-height ratio (-6.57%), waist-to-hip ratio (-4.36%), total body fat (-1.09%), and visceral fat area (-4.6%) decreased significantly in the intervention group. Handgrip strength (+5.46%) and gait speed (+5.71%) improved significantly in the intervention group. The lean body mass increased by 0.35% in the intervention group and by 0.9% in the control group. The femoral neck bone mineral density (-1.45%) and T score (-3.72%) of the control group decreased significantly. The intervention group had more improvement in the status of sarcopenia (OR 1.91) and osteoporosis over the control group. Finally, the intervention group had less deterioration in the status of sarcopenia (OR 0.2) and osteoporosis (OR 0.86) compared with the control group. Conclusion: Our study demonstrated that a 12-week kickboxing exercise training program is effective for improving sarcopenic parameters of muscle strength and function, but not muscle mass in adults, aged 50-85 years. Furthermore, markers of osteoporosis also showed improvement. These findings suggest that a 12-week kickboxing program is effective for muscle and bone health among community-dwelling older individuals.

Association between P1NP and bone strength in postmenopausal women treated with teriparatide.

OBJECTIVE: To evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. MATERIALS AND METHODS: This prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. RESULTS: With teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 µg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. CONCLUSION: P1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.