OBJECTIVE: To evaluate the efficacy and safety of denosumab in the treatment of prostate cancer with bone metastases. METHODS: Relevant studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, Sinomed , CNKI and Wanfang databases. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of included studies, and relevant data were extracted. meta-analysis was performed using RevMan 5.4 and RStudio software, and forest plots were generated. RESULTS: Six randomized controlled trials (RCTs) were included. Compared with the control group, denosumab significantly reduced the risk of skeletal-related events (HR=0.78, 95% CI: 0.62-0.93). In terms of safety, denosumab did not increase the risk of total adverse events, severe adverse events and the adverse events higher than CTC grade 3. CONCLUSION Denosumab can delay the time to first skeletal-related event with good safety. However, due to the limitations of this study, further high-quality, large-sample, multicenter RCTs are needed to confirm these findings.
Humans ; Denosumab/therapeutic use* ; Bone Neoplasms/drug therapy* ; Prostatic Neoplasms/drug therapy* ; Male ; Randomized Controlled Trials as Topic ; Bone Density Conservation Agents/therapeutic use*

OBJECTIVES: To investigate the changes in blood levels of calcium and bone metabolism biochemical markers in patients with primary osteoporosis receiving treatment with denosumab. METHODS: Seventy-three patients with primary osteoporosis treated in our Department between December, 2021 and December 2023 were enrolled. All the patients were treated with calcium supplements, vitamin D and calcitriol in addition to regular denosumab treatment every 6 months. Blood calcium, parathyroid hormone (PTH), osteocalcin (OC), type I procollagen amino-terminal propeptide (PINP), and type I collagen carboxy-terminal telopeptide β special sequence (β‑CTX) data before and at 3, 6, 9, and 12 months after the first treatment were collected from each patient. RESULTS: Three months after the first denosumab treatment, the bone turnover markers (BTMs) OC, PINP, and β-CTX were significantly decreased compared to their baseline levels by 39.5% (P<0.001), 56.2% (P<0.001), and 81.8% (P<0.001), respectively. At 6, 9, and 12 months of treatment, OC, PINP, and β-CTX remained significantly lower than their baseline levels (P<0.001). Blood calcium level was decreased (P<0.05) and PTH level increased (P<0.05) significantly in these patients at months of denosumab treatment, but their levels were comparable to the baseline levels at 6, 9, and 12 months of the treatment (P>0.05). CONCLUSIONS Denosumab can suppress BTMs and has a good therapeutic effect in patients with primary osteoporosis, but reduction of blood calcium and elevation of PTH levels can occur during the first 3 months in spite of calcium supplementation. Blood calcium and PTH levels can recover the baseline levels as the treatment extended, suggesting the importance of monitoring blood calcium and PTH levels during denosumab treatment.
Humans ; Denosumab/therapeutic use* ; Calcium/blood* ; Parathyroid Hormone/blood* ; Biomarkers/blood* ; Osteoporosis/blood* ; Osteocalcin/blood* ; Procollagen/blood* ; Female ; Collagen Type I/blood* ; Peptide Fragments/blood* ; Bone Density Conservation Agents/therapeutic use* ; Bone and Bones/metabolism* ; Male ; Middle Aged ; Vitamin D ; Peptides/blood* ; Aged

INTRODUCTION: A significant treatment gap has been observed in patients with osteoporosis. Our previous audit found a 31.5% rate of anti-osteoporosis medication initiation after fragility fractures at one year. We piloted the use of telecarers to monitor osteoporosis treatment and compliance. METHODS: From January 2017 to January 2018, all hip fracture patients at Changi General Hospital, Singapore, were automatically enrolled into the Health Management Unit valued care hip fracture programme. Telecarer calls were scheduled at discharge, 3, 6 and 12 months. We assessed the acceptability, completion and treatment rates of patients enrolled in this programme. RESULTS: A total of 537 patients with a hip fracture were enrolled in the telecarer programme over one year. Their average age was 79.8 ± 8.23 years, and 63.1% of them were female. A total of 341 patients completed 12 months of follow-up, of which 251 (73.6%) patients were on treatment at 12 months. The most common cause of lack of initiation of secondary osteoporosis treatment was patient or family rejection (34.4%), followed by physician failure to prescribe (24.4%) and renal impairment (24.4%). 16.7% of patients were deemed to have advanced dementia with a life-limiting illness and were, thus, deemed unsuitable for treatment. CONCLUSION Telecarers may be a useful adjunct in the monitoring of osteoporosis treatment after hip fractures in an elderly population. The main limitations are patient or family rejection and physician inertia. Further studies should focus on a combination of interventions for both patients and physicians to increase awareness of secondary fracture prevention.
Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Osteoporotic Fractures/drug therapy* ; Bone Density Conservation Agents/therapeutic use* ; Osteoporosis/drug therapy* ; Hip Fractures/etiology* ; Secondary Prevention

OBJECTIVE: To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA). METHODS: Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 μmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation. RESULTS: The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01). CONCLUSION Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.
Animals ; Berberine/therapeutic use* ; Bone Density Conservation Agents/therapeutic use* ; Bone Plates ; Cartilage, Articular ; Humans ; Ligands ; Male ; NF-kappa B/metabolism* ; Osteoarthritis/metabolism* ; Osteoprotegerin/metabolism* ; RNA, Messenger/therapeutic use* ; Rabbits

Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.
Animals ; Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/therapeutic use* ; Humans ; Reproducibility of Results ; Rodentia

OBJECTIVE: To study and compare the clinical effects of Rehmannia Decoction and alendronate sodium for the treatment of primary osteoporosis. METHODS: From January 2016 to December 2017, 72 patients with primary osteoporosis who took Dihuang Decoction(DHD) orally and alendronate regularly for more than one year were randomly divided into 2 groups:experimental group and control group. The experimental group consisted of 14 males and 22 females, with an average age of(63.97±3.70) years old. The patients in the experimental group took Chinese medicine DHD, one dose each time, one time in the morning and one time in the evening, twice a week. The control group consisted of 16 males and 20 females with an average age of(63.36±3.07) years old. Patients in the control group were given alendronate 70 mg orally once a week. The basic treatment for osteoporosis remained unchanged in both groups(600 mg of calcium carbonate D3 and 0.5 μg of calcitriol capsules were taken daily). Bone mineral density (BMD) of femoral neck and lumbar vertebrae was measured by dual energy X-ray absorptiometry before and after treatment for one year. The levels of serum collagen type I C-terminal peptide (beta-CTX) and serum osteoclast (SOST) were measured before and after treatment for two groups. RESULTS: The age, bone mineral density, SOST and beta-CTX baseline values between the two groups before and after anti-osteoporosis treatment were compared. The difference was not statistically significant(>0.05). Compared with the two groups, the BMD of femoral neck and lumbar vertebrae were increased after 1 year of anti-osteoporosis treatment. The differences were statistically significant (<0.001). The value of serum beta-CTX was significantly lower than before. The values were 52.002 and 50.071 respectively. The value of serum SOST was increased than that before treatment. The values were -29.242 and -30.807 respectively. The differences were statistically significant (<0.001). BMD of the femoral neck and lumbar spine was compared between the two groups after treatment. The P values were 0.294 and 0.478 respectively. The difference was not statistically significant (>0.05). The serum beta-CTX values were compared between the two groups after treatment. The value was 0.908. The serum SOST values were compared between the two groups after treatment. The value was 0.888. The difference was not statistically significant (>0.05). CONCLUSIONS In this study, traditional Chinese medicine DHD is used to treat osteoporosis. It is found that DHD and alendronate have a good effect. The DHD can be used as a choice of Chinese medicine in the treatment of primary osteoporosis.
Absorptiometry, Photon ; Aged ; Alendronate ; therapeutic use ; Bone Density ; Bone Density Conservation Agents ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Osteoporosis ; drug therapy

Medication-related osteonecrosis of the jaw (MRONJ) is a severe complication of bisphosphonates (BPs) or other targeted agent therapies. MRONJ appears as exposed bone, pus, and swelling in the oral and maxillofacial regions. However, neither surgery nor conservative therapy can eliminate symptoms thoroughly. In addition to BPs, several antiresorptive and antiangiogenic agents, such as denosumab and bevacizumab, as well as targeted agents, such as sunitinib and temsirolimus, can cause osteonecrosis of  the  jaw according to the literature. This review aims to summarize the research progress on these new drugs.
Angiogenesis Inhibitors ; therapeutic use ; Bisphosphonate-Associated Osteonecrosis of the Jaw ; drug therapy ; Bone Density Conservation Agents ; adverse effects ; Denosumab ; therapeutic use ; Diphosphonates ; Humans

Alkaline Phosphatase ; metabolism ; Asian Continental Ancestry Group ; Bone Density Conservation Agents ; therapeutic use ; China ; Denosumab ; therapeutic use ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Hyperlipidemias ; complications ; Hypertension ; complications ; Middle Aged ; Osteitis Deformans ; complications ; diagnostic imaging ; drug therapy ; metabolism ; Pelvic Bones ; diagnostic imaging ; Renal Insufficiency, Chronic ; complications ; Singapore ; Tibia ; diagnostic imaging ; Treatment Outcome

Osteoporosis is a major, growing healthcare issue. This is especially of concern in an ageing population like that of Singapore. Osteoporotic patients are at risk of fractures, which can result in increased morbidity and mortality. The use of antiresorptive therapy with bisphosphonates or denosumab has been proven to reduce fracture risk. However, the use of these medications has rarely been associated with the development of osteonecrosis of the jaw, a potentially debilitating condition affecting one or both jaws. Appropriate understanding of the patient's antiresorptive therapy regime, as well as early institution of preventive dental measures, can play an important role in preventing medication-related osteonecrosis of the jaw (MRONJ). Regular monitoring and prompt referral to specialist care is warranted for patients with established MRONJ.
Aged ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Denosumab ; adverse effects ; therapeutic use ; Diphosphonates ; adverse effects ; therapeutic use ; Humans ; Jaw Diseases ; chemically induced ; prevention & control ; Osteonecrosis ; chemically induced ; prevention & control ; Osteoporosis ; complications ; drug therapy ; Osteoporotic Fractures ; complications ; drug therapy ; Risk Factors ; Singapore ; Treatment Outcome

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
Bone Density Conservation Agents/therapeutic use* ; Bone Neoplasms/secondary* ; Denosumab/therapeutic use* ; Diphosphonates/therapeutic use* ; Endothelins/antagonists & inhibitors* ; Humans ; Male ; Prostatic Neoplasms/pathology* ; Protein Kinase Inhibitors/therapeutic use* ; Radioisotopes/therapeutic use* ; Radiopharmaceuticals/therapeutic use* ; Radium/therapeutic use* ; Samarium/therapeutic use* ; Strontium Radioisotopes/therapeutic use*