Alendronate Functionalized Bone-Targeting Pomolic Acid Liposomes Restore Bone Homeostasis for Osteoporosis Treatment.

Introduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem. Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments. Results: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice. Conclusion: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.

Efficacy and safety of minodronate in the treatment of postmenopausal osteoporosis with low back pain: a single-centre, randomized and open-label controlled trial.

BACKGROUND: Low back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients' mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients. METHODS: This is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (< 75 years old) will be at a ratio of 1:2. The primary outcome is the time required for the visual analogue scale (VAS) score to decline by ≥ 10 from baseline. The secondary outcome is the changes in VAS scores from baseline, the frequency and dosage of rescue medication, BTMs, bone mineral density (BMD), and variations in upper gastrointestinal (GI) symptom scores from baseline (including heartburn, pain, and bloating). DISCUSSION: This study will provide objective evidence for the efficiency and safety of minodronate. Furthermore, it will be helpful to evaluate the quantitative relationship between BTMs and BMD in patients with osteoporosis under different ages. TRIAL REGISTRATION: This study protocol has been registered with ClinicalTrials.gov ID NCT05645289 ( https://clinicaltrials.gov/search?term=NCT05645289 ) on December 8, 2022. The registry name is Peking University Third Hospital. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2022465, 2022.08.09, V2.0). The results will be published in scientific peer-reviewed journals. TRIAL STATUS: The protocol was registered at ClinicalTrials.gov (registration number: NCT05645289). Recruitment has started in January 2023 and is still ongoing.

[Dynamics of mandibular density during therapy with zolendronic acid]. / Dinamika plotnosti nizhnei chelyusti v protsesse terapii zolendronovoi kislotoi.

THE AIM OF THE STUDY: Was to investigate the dynamics of mandibular density in cancer patients during therapy with zolendronic acid. MATERIALS AND METHODS: The study comprised 14 patients who received zolendronic acid at a dosage of 4 mg once every 28 days for bone metastases. In all 14 patients, measurements of mandibular density values on CT scans were performed over time. RESULTS: Using multiple linear regression analysis, a model was developed to predict the effect of the number of zolendronic acid injections «X1¼ on the dynamics of mandibular density «Y¼. The resulting formula for predicting mandibular density is Y = 5.9 X1 + 49 HU. CONCLUSION: The model has limitations due to the study design but still can be used by oncologists and dentists to assess mandibular density in patients taking zolendronic acid.

[Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid].

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis.

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.

Effects of differences in dose and frequency of teriparatide on bone structure in Proximal Femur. - Analysis by DXA-based 3D-modeling (3D-SHAPER Software) -TRIPLE-BONE study (The effects of TeRIParatide preparation on bone mineraL density increase and BONE structure).

Trends toward more favorable improvement of the cortical bone parameters by once-weekly (56.5 µg once a week) and twice-weekly teriparatide (28.2 µg twice a week), and that of the trabecular bone parameters by once-daily (1/D) teriparatide (20 µg/day once a day) were shown. PURPOSE: To examine the effects of differences in the amount of teriparatide (TPTD) per administration and its dosing frequency on the bone structure in the proximal femur by dual-energy X-ray absorptiometry (DXA)-based 3D-modeling (3D-SHAPER software). METHODS: This was a multicenter retrospective study. Patients aged 50 years or older with primary osteoporosis who continuously received once-/twice-weekly (1・2/W, n = 60) or 1/D TPTD (n = 14) administration for at least one year were included in the study. Measurement regions included the femoral neck (FN), trochanter (TR), femoral shaft (FS), and total proximal hip (TH). Concurrently, the bone mineral density (BMD) and Trabecular Bone Score (TBS) were measured. RESULTS: The cross-sectional area, cross-sectional moment of inertia, and section modulus in the FS were significantly improved in the 1・2/W TPTD group, as compared to the 1/D TPTD group. However, significant improvement of the cortical thickness and buckling ratio in the FN was observed in the 1/D TPTD group, as compared to the 1・2/W TPTD group. Trabecular BMD values in the FS and TH were significantly increased in the 1/D TPTD group, as compared to the 1・2/W TPTD group, while the cortical BMD values in the TR, FS, and TH were significantly increased in the 1・2/W TPTD group, as compared to the 1/D TPTD group. CONCLUSION: Trends toward more favorable improvement of the cortical bone by 1・2/W TPTD and that of the trabecular bones by 1/D TPTD were observed.

Enhancing osteoporosis treatment using a targeted, sustained-release drug delivery system based on macrocyclic amphiphile.

Osteoporosis, a prevalent systemic bone metabolic disorder, primarily affects postmenopausal women and is characterized by increased bone fragility and a heightened risk of fractures. The efficacy of current osteoporosis treatments is often limited by non-specific drug targeting and undesirable off-target skeletal side effects. To address this challenge, we have developed a novel hydroxyapatite-responsive drug delivery system. This system utilizes a self-assembled p-phosphonatocalix[4]arene tetradodecyl ether (PC4A12C), engineered to specifically target and sustain the release of osteoporosis medication at sites of bone remodeling. Our focus centers on icariin (ICA), a drug known for its potent osteogenic properties and minimal adverse effects. In vitro, ICA-loaded PC4A12C (ICA@PC4A12C) demonstrated enhanced proliferation, differentiation, and mineralization in bone marrow mesenchymal stem cells (BMSCs). In vivo, ICA@PC4A12C exhibited superior efficacy in specifically targeting bone tissue, ensuring a controlled and slow release of icariin directly within the bone environment. In an osteoporosis mouse model, treatment with ICA@PC4A12C showed notable enhancement in osteogenic activity and a significant increase in bone density compared to ICA alone. These results demonstrate the potential of PC4A12C as an effective drug carrier in the development of advanced antiosteoporotic drug delivery systems.

Effects of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate on cortical and trabecular bone of vertebra and proximal femur in postmenopausal women with fragility fracture: Sub-analysis by quantitative computed tomography from the TERABIT study.

PURPOSE: The effects of daily teriparatide (D-PTH, 20 µg/day), weekly high-dose teriparatide (W-PTH, 56.5 µg/week), or bisphosphonate (BP) on the vertebra and proximal femur were investigated using quantitative computed tomography (QCT). METHODS: A total of 131 postmenopausal women with a history of fragility fractures were randomized to receive D-PTH, W-PTH, or bisphosphonate (oral alendronate or risedronate). QCT were evaluated at baseline and after 18 months of treatment. RESULTS: A total of 86 participants were evaluated by QCT (Spine: D-PTH: 25, W-PTH: 21, BP: 29. Hip: PTH: 22, W-PTH: 21, BP: 32. Dropout rate: 30.5 %). QCT of the vertebra showed that D-PTH, W-PTH, and BP increased total vBMD (+34.8 %, +18.2 %, +11.1 %), trabecular vBMD (+50.8 %, +20.8 %, +12.2 %), and marginal vBMD (+20.0 %, +14.0 %, +11.5 %). The increase in trabecular vBMD was greater in the D-PTH group than in the W-PTH and BP groups. QCT of the proximal femur showed that D-PTH, W-PTH, and BP increased total vBMD (+2.8 %, +3.6 %, +3.2 %) and trabecular vBMD (+7.7 %, +5.1 %, +3.4 %), while only W-PTH and BP significantly increased cortical vBMD (-0.1 %, +1.5 %, +1.6 %). Although there was no significant increase in cortical vBMD in the D-PTH group, cortical bone volume (BV) increased in all three treatment groups (+2.1 %, +3.6 %, +3.1 %). CONCLUSIONS: D-PTH had a strong effect on trabecular bone of vertebra. Although D-PTH did not increase cortical BMD of proximal femur, it increased cortical BV. W-PTH had a moderate effect on trabecular bone of vertebra, while it increased both cortical BMD and BV of proximal femur. Although BP had a limited effect on trabecular bone of vertebra compared to teriparatide, it increased both cortical BMD and BV of proximal femur.

MASCC/ISOO Clinical Practice Statement: Adjuvant bone-modifying agents in primary breast cancer patients - prevention of medication-related osteonecrosis of the jaw.

PURPOSE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS raises awareness to the prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with breast cancer treated with adjuvant bone-modifying agents (BMA). METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. RESULTS: In patients treated with adjuvant BMA, dento-alveolar surgery poses a moderate risk for MRONJ that ranges between the high risk for MRONJ in patients with metastatic breast cancer and the low risk for MRONJ in patients with osteoporosis. Existing MRONJ guidelines serve as a starting point for adjuvant BMA use. Urgent procedures should be delivered without delay using the accepted precautions to prevent MRONJ. If elective surgery is considered, the individual risk for MRONJ following surgery should be assessed according to common risk factors. CONCLUSION: Prevention of MRONJ in primary breast cancer patients treated with adjuvant BMA requires risk-benefit assessment; collaboration between the medical team, dental professional, and patient; and patient-specific tailored dental treatment planning. The patient should be informed about this risk. Additional research is needed to define optimal MRONJ care for this population.

Alendronate-functionalized porous nano-crystalsomes mitigate osteolysis and consequent inhibition of tumor growth in a tibia-induced metastasis model.

Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (40.43%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone-targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications.

Poloxamer 407 modified collagen/ß-tricalcium phosphate scaffold for localized delivery of alendronate.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/ß-tricalcium phosphate (ß-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.

Effects of the Application Local Zoledronic Acid On Different Dental Implants in Rats On Osseointegration.

Objective: Recently, a lot of research has been done around the world to popularize the osseointegration of dental implants. In this study, it was investigated the effect of local zoledronic acid application on implants with machined (MAC), resorbable blast materials (RBM), sandblasted and acid-etched (SLA) surface implants integrated in rat tibias. Methodology: A total of 60 female Wistar rats weighing between 270 and 300 g were used in the study. The rats were passing divided into six classes: controls; MAC (n = 10), RBM (n = 10), SLA (n = 10), and local zoledronic acid (LZA) applied groups; LZA-MAC (n = 10), LZA-RBM (n=10) and LZA-SLA (n = 10) and implants were surgically placement into rat tibias in general anesthesia. After a four-week experimental period, the biomechanical bone implant connection level was determined with reverse torque analysis. Results: Osseointegration levels were detected highly in SLA and RBM surface compared with the machined surfaced implants in both control and treatment groups (p < 0.05). Additionally, local application of zoledronic acid in both three groups; implants increased the biomechanic osseointegration level compared with the controls (p < 0.05). Conclusion: In this research, we observe that the local application of the zoledronic acid could increase the osseointegration, and RBM and SLA surface could be better than machined surfaced implants in terms of bone implant connection. In addition, local application of zoledronic acid may be a safer method than systemic application.

Can zoledronic acid reduce the risk of cage subsidence after oblique lumbar interbody fusion combined with bilateral pedicle screw fixation in the elderly population? A retrospective study.

BACKGROUND: The objective of this study was to evaluate the potential of zoledronic acid for reducing the incidence of cage subsidence and enhancing interbody fusion rates following oblique lumbar interbody fusion (OLIF) surgery, particularly as the first reported evidence of the role of zoledronic acid combined with OLIF. METHODS: A retrospective analysis was conducted on data from 108 elderly patients treated for degenerative lumbar diseases using OLIF combined with bilateral pedicle screw fixation from January 2018 to December 2021. Patients were divided into the zoledronic acid (ZOL) group (43 patients, 67 surgical segments) and the control group (65 patients, 86 surgical segments). A comparative analysis of the radiographic and clinical outcomes between the groups was performed, employing univariate and multivariate regression analyses to explore the relationships between cage subsidence and the independent variables. RESULTS: Radiographic outcomes, including anterior height, posterior height, disc height, coronal disc angle, foraminal height, and lumbar lordosis, were not significantly different between the two groups. Similarly, no statistically significant differences were noted in the back visual analog scale (VAS) scores and Oswestry Disability Index (ODI) scores between the groups. However, at the 1-year follow-up, the leg VAS score was lower in the ZOL group than in the control group (P = 0.028). The ZOL group demonstrated a notably lower cage subsidence rate (20.9%) than did the control group (43.0%) (P < 0.001). There was no significant difference in the interbody fusion rate between the ZOL group (93.0%) and the control group (90.8%). Non-use of zoledronic acid emerged as an independent risk factor for cage subsidence (OR = 6.047, P = 0.003), along with lower bone mineral density, lower postoperative anterior height, and concave endplate morphology. The model exhibited robust discriminative performance, with an area under the curve (AUC) of 0.872. CONCLUSION: The administration of zoledronic acid mitigates the risk of cage subsidence following OLIF combined with bilateral pedicle screw fixation in elderly patients; however, it does not improve the interbody fusion rate.

The Effects of Longer Use of Teriparatide on Clinical and Radiographic Outcomes after Spinal Fusion in Geriatric Patients.

Background: Teriparatide is an anabolic agent for osteoporosis and is believed to improve the bone healing process. Previous studies showed that teriparatide could enhance not only fracture healing but also spine fusion. It has been reported that use of teriparatide could promote the spine fusion process and decrease mechanical complications. However, there was no consensus regarding optimal treatment duration. The purpose of this study was to compare surgical outcomes between short-duration and long-duration teriparatide treatment after lumbar fusion surgery in elderly patients. Materials and Methods: All consecutive patients older than 60 years who underwent 1-level lumbar fusion surgery for degenerative diseases between January 2015 and December 2019 were retrospectively reviewed. Based on the duration of teriparatide treatment (daily subcutaneous injection of 20 µg teriparatide), patients were subdivided into two groups: a short-duration (SD) group (<6 months) and a long-duration (LD) group (≥6 months). Mechanical complications, such as screw loosening, cage subsidence, and adjacent vertebral fractures, were investigated. Postoperative 1-year union rate was also evaluated on computed tomography. Clinical outcomes were recorded using visual analog scale (VAS) and Oswestry Disability Index (ODI). Between-group differences for these radiographic and clinical outcomes were analyzed. Results: Ninety-one patients were reviewed in this study, including sixty patients in the SD group and thirty-one patients in the LD group. Their mean age was 72.3 ± 6.2 years, and 79 patients were female. Mean T-score was -3.3 ± 0.8. Cage subsidence (6.7% vs. 3.2%), screw loosening (28.3% vs. 35.5%), and adjacent vertebral fracture (6.7% vs. 9.7%) were not significantly different between the SD and LD groups. Union rate at 1-year postoperative was 65.0% in the SD group and 87.1% in the LD group (p = 0.028). Both groups showed improvement in VAS and ODI after surgery. However, the differences of VAS from preoperative to 6 months and 1 year postoperative were significantly higher in the LD group. Conclusions: Longer teriparatide treatment after lumbar fusion surgery resulted in a higher union rate at 1-year postoperative than the shorter treatment. Also, it could be more beneficial for clinical outcomes.

Cinobufotalin Capsule Combined with Zoledronic Acid in the Treatment of Pain Symptoms and Clinical Efficacy in Prostate Cancer Patients with Bone Metastases: A Retrospective Study.

OBJECTIVE: To retrospectively analyse the effects of cinobufotalin capsule combined with zoledronic acid on pain symptoms and clinical efficacy of prostate cancer patients with bone metastases. METHODS: Patients with prostate cancer with bone metastasis admitted to our hospital from January 2021 to December 2022 were selected as study subjects. They were divided into the control group (treated with zoledronic acid) and the combined group (cinobufotalin capsules were added on the control group basis) according to different recorded treatment methods. The efficacies of the two groups after matching, lumbar L1-4 bone mineral density (BMD), serum calcium, serum phosphorus, visual analogue scale (VAS) score and Karnofsky performance status (KPS) score before and after treatment were compared, and adverse reactions were statistically analysed. RESULTS: A total of 102 patients were included in the study, encompassing 52 patients in the combined group and 50 patients in the control group. After 1:1 preference score matching, 64 patients were included in the two groups. No significant difference in baseline data was found between the two groups (p > 0.05). The total effective rate of the combination group was higher than that of the control group (p < 0.05). No significant differences in L1-4 bone mineral density, serum calcium and phosphorus, VAS score and KPS score were observed between the two groups prior to treatment (p > 0.05). After treatment, the L1-4 bone mineral density (BMD) and KPS score of the combined group decreased to less than those of the control group, the VAS score was lower than that of the control group, and the serum calcium and phosphorus level increased but less than that of the control group (p < 0.05). No significant difference in adverse reactions was found between the two groups (p > 0.05). CONCLUSIONS: Cinobufotalin capsule combined with zoledronic acid had ideal efficacy in the treatment of prostate cancer in patients with bone metastasis. This approach could improve their bone density and quality of life, improve their calcium and phosphorus metabolism, reduce their pain symptoms and provide increased safety. It may have an important guiding role in formulating future clinical treatment plans for patients with prostate cancer and bone metastasis.

Targeted delivery of anti-osteoporosis therapy: Bisphosphonate-modified nanosystems and composites.

Osteoporosis (OP) constitutes a significant health concern that profoundly affects individuals' quality of life. Bisphosphonates, conventional pharmaceuticals widely employed in OP treatment, encounter limitations related to inadequate drug targeting and a short effective duration, thereby compromising their clinical efficacy. The burgeoning field of nanotechnology has witnessed the development and application of diverse functional nanosystems designed for OP treatment. Owing to the bone tissue affinity of bisphosphonates, these nanosystems are modified to address shortcomings associated with traditional drug delivery. In this review, we explore the potential of bisphosphonate-modified nanosystems as a promising strategy for addressing osteoporotic conditions. With functional modification, these nanosystems exhibit a targeted and reversible effect on osteoporotic remodeling, presenting a promising solution to enhance precision in drug delivery. The synthesis methods, physicochemical properties, and in vitro/in vivo performance of bisphosphonate-modified nanosystems are comprehensively examined in this review. Through a thorough analysis of recent advances and accomplishments in this field, we aim to provide insights into the potential applications and future directions of bisphosphonate-modified nanosystems for targeted and reversible osteoporotic remodeling.

The effect of long-term alendronic acid treatment on Modic changes in the lumbar spine: a gender and age-matched study.

BACKGROUND: Low back pain (LBP) affects a significant proportion of the adult population. Potent anti-resorptive drugs such as intravenous zoledronic acid have been demonstrated to reduce Modic changes (MCs) upon magnetic resonance imaging (MRI) of the spine and concomitantly decrease associated LBP. It is uncertain whether oral alendronic acid has a similar effect. METHODS: 82 subjects were recruited in this case-control study. Treatment subjects (n = 41) received oral alendronic acid treatment for at least 1-year and were matched by gender and age (± 2) to control subjects (n = 41) not receiving any anti-osteoporotic medication. The prevalence, type, and extent of MCs were quantified upon T1 and T2-weighted MRIs of the lumbosacral spine. RESULTS: Treatment subjects received oral alendronic acid for 124.0 ± 62.1 weeks at the time of MRI assessment and exhibited a lower prevalence of MCs over the lumbosacral spine (18/41 vs. 30/41, p < 0.001) as compared to control subjects. Amongst both groups, type 2 MCs were predominant. Quantification of type 2 MCs in treatment subjects revealed a significant reduction in area (113 ± 106 mm2 vs. 231 ± 144 mm2, p < 0.01) and volume (453 ± 427 mm3 vs. 925 ± 575 mm3, p < 0.01) affected by type 2 MCs in comparison to matched controls. CONCLUSION: Oral alendronic acid may be useful in the treatment of MC-associated LBP in patients with concomitant osteoporosis.

Does the use of bisphosphonates during pregnancy affect fetal outcomes? A systematic review.

PURPOSE: This systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation. METHODS: A comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs. RESULTS: From an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight. CONCLUSION: Although previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women.