Dose-Dependent Resorption of Allograft by rhBMP-2 Uncompensated by New Bone Formation—A Canine Study With Implants and Zoledronate

Background

Impacted bone allograft is used to restore lost bone in total joint arthroplasties. Bone morphogenetic proteins (BMPs) can induce new bone formation to improve allograft incorporation, but they simultaneously invoke a seemingly dose-dependent allograft resorption mediated by osteoclasts. Bisphosphonates effectively inhibit osteoclast activity. Predicting allograft resorption when augmented with bone morphogenetic protein 2 (BMP-2), we intended to investigate whether a balanced bone metabolism was achievable within a range of BMP-2 doses with systemic zoledronate treatment.

Parathyroid Hormone(1–84) Treatment of Postmenopausal Women with Low Bone Mass Receiving Hormone Replacement Therapy

Treatment of postmenopausal osteoporosis (PMO) is based primarily on antiresorptive agents, including hormone replacement therapy (HT). To evaluate whether anabolic therapy together with HT provides additional benefits in the treatment of PMO, we evaluated the effects of parathyroid hormone (PTH) 1-84 in postmenopausal women with low bone mineral density (BMD) who were receiving chronic (>/=6 months) HT. Subjects were randomized to receive 100 mug PTH(1-84) or placebo injections daily for 24 months (n = 90/group). The primary efficacy outcome was change from baseline in lumbar spine BMD. Secondary end points included changes in hip and distal radius BMD, bone turnover markers, and fracture incidence. The study was terminated early following recommendations regarding HT for PMO. At 18 months, the mean increase in lumbar spine BMD was 7.9% for PTH(1-84) subjects vs. 1.5% for those receiving HT alone; between-group differences were significant at 6 months and persisted throughout the study. Lumbar spine BMD increased in 94% of women receiving PTH(1-84) compared to 59% for HT alone. Femoral neck BMD and bone turnover markers were significantly higher in PTH(1-84)-treated subjects, but the changes in total hip and distal radius BMD were not significant. PTH(1-84) treatment was generally well-tolerated, with hypercalciuria, hypercalcemia, nausea, vomiting, and dizziness reported more frequently in the HT + PTH(1-84) group. In conclusion, addition of PTH(1-84) to stable HT produced marked increases in lumbar spine BMD and may represent an additional approach to the treatment of PMO women receiving HT.     

Bone marrow fibrosis with fibrocytic and immunoregulatory responses induced by β-catenin activation in osteoprogenitors

Wnt/β-catenin signaling has been reported to contribute to the development of bone fibrous dysplasia. However, it remains unclear whether fibrocytes and immune cells are involved in this β-catenin-mediated bone marrow fibrosis. In this study, we showed that constitutive activation of β-catenin by Col1a1-Cre (3.6-kb) exhibited bone marrow fibrosis, featured with expanded populations of fibrocytes, myofibroblasts and osteoprogenitors. Lineage tracing and IHC examinations showed that Col3.6-Cre display Cre recombinase activity not only in osteoprogenitors, but also in monocyte-derived fibrocytes in the endosteal niches of bones. Additionally, β-catenin stimulated the secretion of cytokines and pro-fibrotic signals in bone marrow, including GM-CSF, TGFβ1 and VEGF. Consequently, the frequency of differentiated immature monocyte-derived dendritic cells and naïve T cells was markedly increased in the mutant bone marrow. These phenotypes were quite different from those following β-catenin activation in mature osteoblasts driven by Col1a1-Cre (2.3-kb). Our findings suggested that a conserved pro-fibrotic signal cascade might underlie β-catenin-mediated bone marrow fibrosis, involving TGFβ1-enhanced fibrocyte activation and immunoregulatory responses. This study might shed new light on the understanding and development of a therapeutic strategy for bone fibrous dysplasia.     

Prevention of Bone Cement Displacement in Kümmell Disease without Neurological Deficits through Treatment with a Novel Hollow Pedicle Screw Combined with Kyphoplasty

Objective

Displacement of bone cement following percutaneous vertebral augmentation for Kümmell disease (KD) presents a significant concern, resulting in increasing back pain and compromising daily activities. Unfortunately, current literature does not yet establish a validated and minimally invasive surgical intervention for this issue. This study aims to investigate the effects of a novel hollow pedicle screw combined with kyphoplasty (HPS-KP) in preventing bone cement displacement following simply percutaneous kyphoplasty for the management of KD.

Methods

A total of 22 patients (six males, 16 females, averagely aged 77.18 ± 7.63 years) with KD without neurological deficits treated by HPS-KP at the hospital between March 2021 and June 2022 were hereby selected, among which, there were three stage I KD cases, 12 stage II KD cases, and seven stage III KD cases according to Li's classification. Bone mineral density (BMD), spinal X-ray, computed tomography (CT), and magnetic resonance imaging (MRI) were examined before the operation. The operation time, intraoperative blood loss, and postoperative complications were all recorded. The follow-up focused on visual analog scale (VAS) score, Oswestry dysfunction index (ODI), anterior vertebral height (AVH), middle vertebral height (MVH), posterior vertebral height (PVH), wedge-shape affected vertebral Cobb angle (WCA), and bisegmental Cobb angle (BCA). One-way analysis of variance (ANOVA) followed by Bonferroni post-hoc test was employed for performing multiple comparisons in the present study.

Results

All patients having received the operation successfully were followed up for more than 8 months (ranging from 8 to 18 months). The operation time, intraoperative blood loss, and BMD (T-score) were 39.09 ± 5.64 min, 14.09 ± 3.98 ml, and − 3.30 ± 0.90 g/cm³, respectively. Statistically significant differences were observed in the VAS score, ODI, AVH, MVH, and WCA (All p < 0.05), but there was no statistically significant difference in PVH and BCA at different time points (All p > 0.05). During follow-up, five patients suffered from bone cement leakage, and one presented an adjacent vertebral fracture and no bone cement displacement.

Conclusion

HPS-KP could be safe and effective in the treatment of KD without neurological deficits, effectively relieving the symptoms of patients, restoring partial vertebral height, and preventing the occurrence of bone cement displacement.     

Improvement of periarticular osteoporosis in postmenopausal women with rheumatoid arthritis by β-alanyl-l-histidinato zinc: a pilot study

The effect of zinc on bone metabolism in patients with rheumatoid arthritis (RA) is unknown. In the present pilot study, we investigated the effect of two antiulcer drugs, β-alanyl-l-histidinato zinc (AHZ) and cimetidine, on bone metabolism in postmenopausal women with RA who had bilateral wrist pain. Eight patients were enrolled in a prospective, single-blind study consisting of 6-month cimetidine treatment (400 mg/day) followed by 6-month AHZ treatment (300 mg/day). Biochemical markers and bone mineral density (BMD) by dual energy X-ray absorptiometry were measured at baseline, 6 months, and 12 months. Three patients withdrew, and five patients (mean age 60; range 55–64 years) were analyzed. Their disease activity including wrist pain and dosages of prednisolone and disease-modifying antirheumatic drugs remained unchanged during the 12-month treatment. The AHZ treatment increased serum zinc (AHZ vs cimetidine, +48.0% vs +5.6%), and resulted in significant increases of serum bone-specific alkaline phosphatase (+93.5% vs−14.7%) and BMD of the bilateral ultradistal radius (+4.9% vs−5.6%). However, the AHZ treatment had no effect on BMD of the lumbar spine (−2.0% vs +1.5%) or the bilateral distal third of radius (−2.1% vs +0.2%). In the AHZ treatment, the percentage change in BMD of the unilateral ultradistal radius with more severe wrist pain was positively correlated with the percentage change in serum zinc (r = 0.97). These findings suggest for the first time that AHZ treatment improves periarticular osteoporosis, probably through an increase of bone formation, in postmenopausal women with RA. Randomized double-blind controlled trials are needed. Received: March 13, 2000 / Accepted: May 22, 2000     

Prospective Study of a Two-Stage Operative Concept in the Treatment of Morbid Obesity: Primary Lap-Band® Followed if Needed by Sleeve Gastrectomy with Duodenal Switch

Background We investigated the success rate of a twostage operative concept for treatment of morbid obesity: primary laparoscopic adjustable gastric banding (LAGB, Lap-Band?) for all morbidly obese patients, followed by sleeve gastrectomy with biliopancreatic diversion (duodenal switch or DS) in case of failure. Methods From Dec 1996 to May 2004, 366 consecutive patients (female 78%, mean age 41 (17–66) years, BMI 44.3 (35–75) kg/m² were prospectively evaluated, using the two-stage operative concept. The follow-up rate after a mean of 4.1 (1–8.4) years was 98%. Primary outcome measure was BAROS score, defined according to weight loss, quality of life, reduction in co-morbidities, complications and re-operations. Results A very good-to-excellent result was found in 118 patients (32%), 141 (39%) had a goodresults, 76 (21%) a fair result, and 31 (8%) were failures. 39 patients needed re-banding due to slippage, 68 a DS, and 11 patients had band removal. Early morbidity of the Lap-Band? was 3.8%, that of DS 13%, and mortality was zero.The excess weight loss at last follow-up of all the patients was 44% (40% after Lap-Band?/rebanding, and 82% 2 years after DS). Conclusion The two-stage concept with primary LAGB, followed by DS in case of failure, leads to a good result in 71% of morbidly obese patients. LAGB alone does not appear to be an adequate procedure for every morbidly obese patient.     

Vibegron,a Novel Potent and Selective β3-Adrenoreceptor Agonist,for the Treatment of Patients with Overactive Bladder: A Randomized,Double-blind,Placebo-controlled Phase 3 Study

Background

Vibegron is a novel, potent, and selective β₃-adrenoreceptor agonist for the treatment of patients with overactive bladder (OAB).