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Trials Dec 2023Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear...
Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial.
BACKGROUND
Participants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes.
METHODS
This is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ - 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100-125 mg/dL, (ii) a 2-hour plasma glucose level of 140-199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7-6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months.
DISCUSSION
This study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations.
TRIAL REGISTRATION
This study had been registered in the Chinese Clinical Trials Registry.
REGISTRATION NUMBER
ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn .
Topics: Female; Humans; Blood Glucose; Bone Density; Bone Density Conservation Agents; Denosumab; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Multicenter Studies as Topic; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Prediabetic State; Randomized Controlled Trials as Topic; RANK Ligand
PubMed: 38111052
DOI: 10.1186/s13063-023-07769-0 -
International Journal of Molecular... May 2024Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity...
Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the gene, is associated with reduced gene transcription. This study evaluates the variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) ( = 20) and non-responders (OP-NR) ( = 40). We observed an association of CC genotype with treatment failure ( = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; = 0.026) and TH (CC = -2.06% ± 1.84; = 0.015) after two years of alendronate sodium treatment. Relative expression of the gene was also evaluated in OP-R and OP-NR patients. Higher expression of the gene was also observed in OP-NR group (FC = 1.84 ± 0.77; = 0.006) when compared to OP-R. In conclusion, the influence observed of expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.
Topics: Humans; Alendronate; Bone Density; Female; Geranyltranstransferase; Male; Osteoporosis; Aged; Treatment Failure; Middle Aged; Polymorphism, Single Nucleotide; Bone Density Conservation Agents; Genotype; Alleles; Case-Control Studies
PubMed: 38891810
DOI: 10.3390/ijms25115623 -
Archives of Osteoporosis May 2024This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who... (Observational Study)
Observational Study
UNLABELLED
This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who do receive treatment, and more than one-quarter having no follow-up visits post-fracture. These data highlight the need to improve secondary fracture prevention in primary care.
PURPOSE
To describe osteoporosis (OP) treatment patterns and follow-up in subjects with fragility fracture seen in Spanish primary care (PC).
METHODS
This observational, retrospective chart review included subjects aged ≥ 70 years listed in the centers' records (November 2018 to March 2020), with ≥ 1 fragility fracture and prior consultation for any reason; subjects who had participated in another study were excluded. Outcomes included OP treatments and follow-up visits post-fragility fracture.
RESULTS
Of 665 subjects included, most (87%) were women; overall mean (SD) age, 82 years. Fewer than two thirds (61%) had received any prior OP treatment (women, 65%; men, 38%); of these, 38% had received > 1 treatment (women, 25%; men, 13%). Among treated subjects, the most frequent first-line treatments were alendronate (43%) and RANKL inhibitor denosumab (22%), with a higher discontinuation rate and shorter treatment duration observed for alendronate (discontinuation, 42% vs 16%; median treatment duration, 2.5 vs 2.1 years). Over one-quarter (26%) of subjects had no follow-up visits post-fragility fracture, with this gap higher in women than men (35% versus 25%). The most common schedule of follow-up visits was yearly (43% of subjects with a fragility fracture), followed by half-yearly (17%) and biennial (10%), with a similar trend in men and women. Most OP treatments were prescribed by PC physicians, other than teriparatide and zoledronate.
CONCLUSIONS
Across Spanish PC, we observed a large gap in the treatment and follow-up of elderly subjects experiencing a fragility fracture. Our data highlights the urgent need to improve secondary fracture prevention in PC.
Topics: Humans; Female; Male; Aged; Spain; Aged, 80 and over; Secondary Prevention; Retrospective Studies; Primary Health Care; Bone Density Conservation Agents; Osteoporotic Fractures; Osteoporosis; Alendronate; Denosumab
PubMed: 38722400
DOI: 10.1007/s11657-024-01394-3 -
MDM Policy & Practice 2023To conduct cost-utility analyses for Computed Tomography To Strength (CT2S), a novel osteoporosis screening service, compared with dual-energy X-ray absorptiometry...
Cost-Effectiveness Analysis of CT-Based Finite Element Modeling for Osteoporosis Screening in Secondary Fracture Prevention: An Early Health Technology Assessment in the Netherlands.
UNLABELLED
To conduct cost-utility analyses for Computed Tomography To Strength (CT2S), a novel osteoporosis screening service, compared with dual-energy X-ray absorptiometry (DXA), treat all without screening, and no screening methods for Dutch postmenopausal women referred to fracture liaison service (FLS). CT2S uses CT scans to generate femur models and simulate sideways fall scenarios for bone strength assessment. Early health technology assessment (HTA) was adopted to evaluate CT2S as a novel osteoporosis screening tool for secondary fracture prevention. We constructed a 2-dimensional simulation model considering 4 strategies (no screening, treat all without screening, DXA, CT2S) together with screening intervals (5 y, 2 y), treatments (oral alendronate, zoledronic acid), and discount rate scenarios among Dutch women in 3 age groups (60s, 70s, and 80s). Strategy comparisons were based on incremental cost-effectiveness ratios (ICERs), considering an ICER below €20,000 per QALY gained as cost-effective in the Netherlands. Under the base-case scenario, CT2S versus DXA had estimated ICERs of €41,200 and €14,083 per QALY gained for the 60s and 70s age groups, respectively. For the 80s age group, CT2S was more effective and less costly than DXA. Changing treatment from weekly oral alendronate to annual zoledronic acid substantially decreased CT2S versus DXA ICERs across all age groups. Setting the screening interval to 2 y increased CT2S versus DXA ICERs to €100,333, €55,571, and €15,750 per QALY gained for the 60s, 70s, and 80s age groups, respectively. In all simulated populations and scenarios, CT2S was cost-effective (in some cases dominant) compared with the treat all strategy and cost-saving (more effective and less costly) compared with no screening. CT2S was estimated to be potentially cost-effective in the 70s and 80s age groups considering the willingness-to-pay threshold of the Netherlands. This early HTA suggests CT2S as a potential novel osteoporosis screening tool for secondary fracture prevention.
HIGHLIGHTS
For postmenopausal Dutch women who have been referred to the FLS, direct access to CT2S may be cost-effective compared with DXA for age groups 70s and 80s, when considering the ICER threshold of the Netherlands. This study positions CT2S as a potential novel osteoporosis-screening tool for secondary fracture prevention in the clinical setting.A shorter screening interval of 2 y increases the effectiveness of both screening strategies, but the ICER of CT2S compared with DXA also increased substantially, which made CT2S no longer cost-effective for the 70s age group; however, it remains cost-effective for individuals in their 80s.Annual zoledronic acid treatment with better adherence may contribute to a lower cost-effectiveness ratio when comparing CT2S to DXA screening and the treat all strategies for all age groups.
PubMed: 37900721
DOI: 10.1177/23814683231202993 -
Scientific Reports Nov 2023Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid...
Osteoarthritis (OA) is a chronic degenerative joint disease characterized by pain and cartilage damage. Intra-articular (i.a) viscosupplementation with hyaluronic acid (HA) is frequently used for the management of OA. Preclinical studies have reported that bisphosphonates (BPs) may have a therapeutic potential to slow down or reverse the progression of OA. Among these, alendronate (ALN) has demonstrated chondroprotective effects in both in vitro and vivo experiments. This study evaluated the effects of a novel alendronate-hyaluronic acid (ALN-HA) conjugate on an OA in vivo model induced by medial meniscus destabilization (DMM). DMM surgery was performed on the knees of Sprague Dawley rats that received, after four weeks, one intra-articular (i.a.) injection of: (1) ALN-HA; (2) HA; (3) sodium chloride (NaCl). Sham-operated rats were used as control. Allodynia was assessed by Von Frey test. Joint degeneration was evaluated eight weeks after treatment by micro-computed tomography (micro-CT), histology, and immunohistochemistry. Collagen cross-linked C-telopeptides (CTX-I and CTX-II) serum levels were determined by ELISA. Paw withdrawal threshold increased in ALN-HA group when compared to rats treated with NaCl or HA. Micro-CT did not show differences between ALN-HA, HA and NaCl groups. ALN-HA injection produced significant improvements in articular cartilage degeneration showing an OARSI score lower than those of HA and NaCl, and reduced matrix metalloproteinase (MMP)-13, MMP-3, interleukin-6, vascular endothelial growth factor and Caspase-3 expression. CTX-I was reduced after ALN-HA treatment when compared to NaCl. Our results indicate that i.a. use of ALN after conjugation with HA limits OA development and progression in the rat DMM model, and may lead to the development of novel therapeutic strategies in OA management.
Topics: Rats; Animals; Hyaluronic Acid; Alendronate; Menisci, Tibial; Sodium Chloride; X-Ray Microtomography; Vascular Endothelial Growth Factor A; Rats, Sprague-Dawley; Osteoarthritis; Injections, Intra-Articular; Cartilage, Articular; Disease Models, Animal
PubMed: 38001135
DOI: 10.1038/s41598-023-46965-5 -
AACE Clinical Case Reports 2023Osteogenesis imperfecta (OI) is a genetic disorder that affects type 1 collagen synthesis causing increased bone fragility, low bone mass, and skeletal deformity....
BACKGROUND/OBJECTIVE
Osteogenesis imperfecta (OI) is a genetic disorder that affects type 1 collagen synthesis causing increased bone fragility, low bone mass, and skeletal deformity. Bisphosphonates are recommended for treatment of OI patients; however, the efficacy of sclerostin inhibitors such as romosozumab has not been determined in OI patients with osteoporosis.
CASE REPORT
A 52-year-old G2P2 clinically diagnosed with OI, with a history of multiple fractures beginning in childhood presented with low bone mass. On physical examination, blue sclera was observed. She was previously treated with alendronate therapy from April 2014 to June 2015 without significant improvement in bone mineral density (BMD). After the onset of menopause, she began romosozumab 210 mg subcutaneous therapy once a month for 12 months. Repeat dual-energy X-ray absorptiometry showed an increase of 10.3% in BMD of the spine and a 5.4% increase in BMD of the right hip. The trabecular bone score increased by 5.2%.
DISCUSSION
Current literature is limited regarding the use of sclerostin inhibitors in OI patients. Our patient's improvement in BMD of the spine and right hip after romosozumab therapy was significant at a 95% confidence level, compared to treatment initiation. Her trabecular bone score also improved significantly. Six months into our patient's treatment course, a case in Japan of a male with severe osteoporotic OI and recurrent fractures showed improvement in BMD after romosozumab therapy.
CONCLUSION
This case highlights our patient's significant response to romosozumab and warrants further investigation of romosozumab as a potential treatment option for OI patients with osteoporosis.
PubMed: 38045794
DOI: 10.1016/j.aace.2023.10.002 -
Frontiers in Immunology 2023Osteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced...
INTRODUCTION
Osteoporosis, one of the most common non-communicable human diseases worldwide, is one of the most prevalent disease of the adult skeleton. Glucocorticoid-induced osteoporosis(GIOP) is the foremost form of secondary osteoporosis, extensively researched due to its prevalence.Probiotics constitute a primary bioactive component within numerous foods, offering promise as a potential biological intervention for preventing and treating osteoporosis. This study aimed to evaluate the beneficial effects of the probiotic on bone health and its underlying mechanisms in a rat model of glucocorticoid dexamethasone-induced osteoporosis, using the osteoporosis treatment drug alendronate as a reference.
METHODS
We examined the bone microstructure (Micro-CT and HE staining) and analyzed the gut microbiome and serum metabolome in rats.
RESULTS AND DISCUSSION
The results revealed that treatment significantly restored parameters of bone microstructure, with elevated bone density, increased number and thickness of trabeculae, and decreased Tb.Sp. Gut microbiota sequencing results showed that probiotic treatment increased gut microbial diversity and the ratio of Firmicutes to Bacteroidota decreased. Beneficial bacteria abundance was significantly increased (_NK4A136_group, , , , and _R_7_group), and harmful bacteria abundance was significantly decreased (). According to the results of serum metabolomics, significant changes in serum metabolites occurred in different groups. These differential metabolites were predominantly enriched within the pathways of Pentose and Glucuronate Interconversions, as well as Propanoate Metabolism. Furthermore, treatment of significantly increased serum levels of Pyrazine and gamma-Glutamylcysteine, which were associated with inhibition of osteoclast formation and promoting osteoblast formation. can protect rats from DEX-induced GIOP by mediating the "gut microbial-bone axis" promoting the production of beneficial bacteria and metabolites. Therefore is a potential candidate for the treatment of GIOP.
Topics: Adult; Humans; Animals; Rats; Gastrointestinal Microbiome; Glucocorticoids; Lactobacillus plantarum; Metabolome; Osteoporosis; Clostridiales
PubMed: 38264658
DOI: 10.3389/fimmu.2023.1285442 -
The American Journal of Case Reports Oct 2023BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related...
BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.
Topics: Female; Humans; Middle Aged; Diphosphonates; Alendronate; Osteoporosis, Postmenopausal; Bone Density Conservation Agents; Mandibular Fractures; Osteoporosis; Fractures, Spontaneous; Femoral Fractures; Osteomyelitis
PubMed: 37867315
DOI: 10.12659/AJCR.941144 -
Medicine Nov 2023Vertebroplasty (VP) effectively treats vertebral compression fractures (VCFs). However, the issue of secondary new VCFs (SNVCFs) after VP is yet to be addressed....
Vertebroplasty (VP) effectively treats vertebral compression fractures (VCFs). However, the issue of secondary new VCFs (SNVCFs) after VP is yet to be addressed. Therefore, identification of risk factors for SNVCFs after VP may aid the development of strategies to minimize SNVCF risk. This study aimed to retrospectively evaluate risk factors for SNVCFs after VP, including those associated with the type of anti-osteoporotic treatment administered after VP. Data from 128 patients who underwent single-level VP were collected and reviewed. Patients were divided into 2 groups: those with (n = 28) and without (n = 100) SNVCF within 1 year of VP. We collected the following patient data: age, sex, site of compression fracture, medical history, bone mineral density (BMD), history of long-term steroid use, history of osteoporosis drug use, duration between fracture and VP, VP implementation method (unilateral or bilateral), cement usage in VP, cement leakage into the disc, compression ratio before VP, pre- and postoperative recovery ratio of the lowest vertebral body height, and kyphotic angle of fractured vertebrae. These data were analyzed to identify factors associated with SNVCFs after VP and to investigate the effects of the type of anti-osteoporotic treatment administered for SNVCFs. SNVCFs occurred in 28 patients (21.9%) within 1 year of VP. Logistic regression analysis identified BMD, cement leakage into the disc, and long-term steroid use to be significantly associated with the occurrence of SNVCFs. The group treated with zoledronate after VP had a significantly reduced SNVCF incidence compared with the group treated with calcium (P < .001). In addition, the zoledronate group had a lower SNVCF incidence compared with the groups treated with alendronate (P = .05), selective estrogen receptor modulators (P = .26), or risedronate (P = .22). This study showed that low BMD, presence of an intradiscal cement leak, and long-term steroid use were risk factors for developing SNVCFs following VP. Additionally, among osteoporosis treatments prescribed for VP, zoledronate may be the preferred choice to reduce the risk of SNVCFs.
Topics: Humans; Fractures, Compression; Retrospective Studies; Spinal Fractures; Osteoporotic Fractures; Zoledronic Acid; Osteoporosis; Vertebroplasty; Risk Factors; Bone Cements; Steroids; Treatment Outcome
PubMed: 38013362
DOI: 10.1097/MD.0000000000035042 -
Medicina Oral, Patologia Oral Y Cirugia... Dec 2023To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
BACKGROUND
To access the occurrence of bisphosphonate-associated osteonecrosis of the jaw (BAONJ) in individuals with rheumatoid arthritis (RA).
MATERIAL AND METHODS
Observational studies that evaluated the occurrence of BAONJ in individuals with RA (BAONJ-RA) were considered for inclusion. Electronic searches were performed up to December 2022 in six databases and in the grey literature. The study selection, data extraction, and quality assessment of the included studies according to the Joanna Briggs Institute Critical Appraisal Checklists was performed. The certainty of evidence was evaluated using the GRADE approach.
RESULTS
Five studies were included three cohort and two cross-sectional. The sample size of subjects with RA ranged from 16 to 3201. Together, the studies presented 36 cases of BAONJ-RA. Prevalence of BAONJ-RA ranged from 0.094% to 56.25%. The incidence ranged from 0.4% to 2.21. Women between the 6th and 8th decade of life were the most affected. Alendronate (n=5) and zoledronic acid (n=9), orally and intravenously, respectively, were the most used bisphosphonates. The duration of bisphosphonates use ranged from 2.7 to 8 years. The certainty of evidence was very low.
CONCLUSIONS
The occurrence of BAONJ-RA is low. However, the certainty of the evidence was very low for this outcome.
PubMed: 38150601
DOI: 10.4317/medoral.26373