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Journal of Pediatric Endocrinology &... Apr 2006
Topics: Humans; Alendronate; Child; Adolescent; Osteoporosis; Bone Density Conservation Agents; Female; Administration, Oral; Male; Bone Density; Treatment Outcome
PubMed: 38742779
DOI: 10.1515/jpem-2006-190410 -
Expert Opinion on Investigational Drugs 2023Pharmacological strategies might influence bone healing in terms of time to union or quality of mature bone. This expert opinion discussed the current level I evidence... (Review)
Review
INTRODUCTION
Pharmacological strategies might influence bone healing in terms of time to union or quality of mature bone. This expert opinion discussed the current level I evidence on the experimental pharmacological agents used to favor bone fracture healing.
AREAS COVERED
This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the 2020 PRISMA statement. In April 2023, the following databases were accessed: PubMed, Web of Science, Google Scholar, Embase. All the randomized clinical trials investigating pharmacological agents for bone fracture healing were accessed. No time constraint was set for the search. The search was restricted to RCTs. No additional filters were used in the database search. Data from 19 RCTs (4067 patients) were collected. 78% (3160 of 4067) were women. The mean length of the follow-up was 9.3 months (range, 1-26 months). The mean age of the patients was 64.4 years (range, 8-84 years).
EXPERT OPINION
Calcitonin could favor bone fracture healing. Bisphosphonates (alendronate, zoledronate, clodronate), monoclonal antibodies (denosumab, romosozumab), statins, vitamin D and calcium supplementation, strontium ranelate, and ibuprofen did not influence bony healing. Concerning the effect of parathormone, current level I evidence is controversial, and additional studies are required.
LEVEL OF EVIDENCE
Level I, systematic review of RCTs.
Topics: Humans; Female; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Male; Fracture Healing; Bone Density Conservation Agents; Diphosphonates; Alendronate; Vitamin D
PubMed: 37740660
DOI: 10.1080/13543784.2023.2263352 -
ACS Biomaterials Science & Engineering Dec 2023The development of magnesium-derived biomaterials is one of the most promising research in bone tissue engineering, and related strategies have been extensively used for...
The development of magnesium-derived biomaterials is one of the most promising research in bone tissue engineering, and related strategies have been extensively used for tendon, skull, cartilage, and bone regeneration. Also, alendronate, a well-recognized drug for osteoporosis treatment, has recently attracted a great deal of attention for bone repair. However, rapid corrosion of Mg and low systemic bioavailability of alendronate are the main limitations hampering their full exploitation. In this work, by means of physical and chemical cross-linking conjugating magnesium-metal-organic frameworks (Mg-MOFs) and bone-targeting alendronate to biocompatible gelatin scaffolds, a facile method is developed for the preparation of organic/inorganic nanocomposite gel scaffolds. The results affirmed that the nanocomposite gel scaffolds possessed excellent biocompatibility, continuous slow release of Mg and alendronate, strong bone affinity, and bone regeneration. It is noteworthy that the continuous slow release of Mg and alendronate could induce the macrophage switch to the M2 phenotype and promote osteogenic differentiation in the early stage, resulting in improved bone regeneration during implanting the scaffolds into the distal femoral. In summary, Mg-MOFs-loaded alendronate-modified gelatin gel scaffolds have been developed, exhibiting great potential for bone regenerative.
Topics: Diphosphonates; Osteogenesis; Alendronate; Magnesium; Gelatin; Nanogels; Tissue Scaffolds; Bone Regeneration
PubMed: 37942941
DOI: 10.1021/acsbiomaterials.3c01080 -
Pharmacotherapy Sep 2023To compare the effect of denosumab and alendronate on bone mineral density (BMD) in renal transplant recipients (RTRs) with low bone mass. (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To compare the effect of denosumab and alendronate on bone mineral density (BMD) in renal transplant recipients (RTRs) with low bone mass.
METHODS
Patients were randomized to receive either denosumab subcutaneously (60 mg/6 months), oral alendronate (70 mg/week), or no treatment for 1 year. The three groups were prescribed daily calcium and vitamin D. Primary outcome was BMD assessed at lumbar spine, hip, and radius and measured by dual-energy X-ray absorptiometry (DEXA) at baseline and after 6 and 12 months. Adverse events and laboratory assessments (calcium, phosphate, vitamin D, renal functions, and intact parathyroid hormone) were monitored for all patients. Quality of life was assessed at baseline and after 6 and 12 months for all patients.
RESULTS
Ninety RTRs were included in the study (30 in each group). Baseline clinical characteristics and BMD values were comparable in the three groups. After 12 months, lumbar spine T-score of patients treated with denosumab and alendronate showed a median increase of 0.5 [95% confidence interval (CI): 0.4-0.6] and 0.5 (95% CI: 0.4-0.8), respectively, and patients in the control group showed a decrease of -0.2 (95% CI: -0.3 to -0.1), p < 0.001. Denosumab and alendronate showed a significant comparable gain in T-scores at hip and radius versus a significant decrease in the control group. Adverse events and laboratory values were similar in the three groups. Both treatments resulted in comparable significant improvement in physical functioning, physical role limitations, vitality, and pain scores.
CONCLUSION
Denosumab and alendronate showed comparable efficacy in improving BMD at all measured skeletal sites and were safe and well-tolerated, with no serious adverse effects reported in RTRs with low bone mass. The study was registered on ClinicalTrials.gov, number NCT04169698.
Topics: Humans; Alendronate; Denosumab; Bone Density Conservation Agents; Bone Density; Kidney Transplantation; Calcium; Quality of Life; Vitamin D
PubMed: 37323099
DOI: 10.1002/phar.2838 -
The Lancet Regional Health. Europe Jul 2023Although age-standardised hip fracture incidence has declined in many countries during recent decades, the number of fractures is forecast to increase as the population...
BACKGROUND
Although age-standardised hip fracture incidence has declined in many countries during recent decades, the number of fractures is forecast to increase as the population ages. Understanding the drivers behind this decline is essential to inform policy for targeted preventive measures. We aimed to quantify how much of this decline could be explained by temporal trends in major risk factors and osteoporosis treatment.
METHODS
We developed a new modelling approach, Hip-IMPACT, based on the validated IMPACT coronary heart disease models. The model applied sex- and age stratified hip fracture numbers and prevalence of pharmacologic treatments and risk/preventive factors in 1999 and 2019, and best available evidence for independent relative risks of hip fracture associated with each treatment and risk/preventive factor.
FINDINGS
Hip-IMPACT explained 91% (2500/2756) of the declining hip fracture rates during 1999-2019. Two-thirds of the total decline was attributed to changes in risk/preventive factors and one-fifth to osteoporosis medication. Increased prevalence of total hip replacements explained 474/2756 (17%), increased body mass index 698/2756 (25%), and increased physical activity 434/2756 (16%). Reduced smoking explained 293/2756 (11%), and reduced benzodiazepine use explained (366/2756) 13%. Increased uptake of alendronate, zoledronic acid, and denosumab explained 307/2756 (11%), 104/2756 (4%) and 161/2756 (6%), respectively. The explained decline was partially offset by increased prevalence of type 2 diabetes and users of glucocorticoids, z-drugs, and opioids.
INTERPRETATION
Two-thirds of the decline in hip fractures from 1999 to 2019 was attributed to reductions in major risk factors and approximately one-fifth to osteoporosis medication.
FUNDING
The Research Council of Norway.
PubMed: 37215491
DOI: 10.1016/j.lanepe.2023.100643 -
The Saudi Dental Journal Jul 2023Periodontitis is a complex chronic inflammatory disease aggravated in immunosuppressed patients. However, adjuvant therapies can alleviate severe inflammation and slow...
BACKGROUND
Periodontitis is a complex chronic inflammatory disease aggravated in immunosuppressed patients. However, adjuvant therapies can alleviate severe inflammation and slow down disease progression.
OBJECTIVE
To evaluate the efficacy of myricitrin, a herbal flavonoid glycoside, in reducing immunosuppression-associated periodontitis and compare its effects with that of alendronate on alveolar bone regeneration.
METHODS
Fifty albino Wistar rats were randomly allocated to the control, periodontitis, immunosuppressant, myricitrin, and alendronate groups. Ligature-associated periodontitis was induced in all groups, except the control group. Cyclosporin A (CsA) was administered subcutaneously in the immunosuppressant group for immunosuppression. The myricitrin group received CsA and myricitrin, whereas the alendronate group received CsA and alendronate. The therapeutic efficacies of myricitrin and alendronate were compared histologically, morphometrically, and biochemically.
RESULTS
Myricitrin reversed bone destruction in the periodontitis and immunosuppressant groups. Morphometrically, myricitrin showed comparable improvements to alendronate in terms of gaining more bone area to 49.4 ± 4.6 and 59.5 ± 2%, respectively ( < 0.001 in relation to the untreated periodontitis group). Concomitantly, myricitrin increased osteoblast count significantly to 28.4 ± 4.7 closer to the 34.5 ± 2.4 count in the alendronate group ( < 0.001 compared with 22.5 ± 2.6 count of the immunosuppressant group). Moreover, myricitrin restored the serum calcium to 9.4 ± 0.6 mg/dL and alkaline phosphatase up to 112.9 ± 2.9 IU/L, which were almost normal levels similar to the control cohort ( > 0.05).
CONCLUSION
Myricitrin showed beneficial effects in counteracting bone resorption in subjects with immunosuppression-associated periodontitis. Its efficacy in slowing down disease progression was comparable to that of alendronate.
PubMed: 37520591
DOI: 10.1016/j.sdentj.2023.04.002 -
British Journal of Clinical Pharmacology Aug 2023Despite 2 h of daily exercise training, muscle wasting and bone loss are still present after 6-month missions to the international space station. Some crew members... (Review)
Review
Despite 2 h of daily exercise training, muscle wasting and bone loss are still present after 6-month missions to the international space station. Some crew members lose bone much faster than others. In preparation for missions to the Moon and Mars, space agencies are therefore reviewing their countermeasure portfolios. Here, we discuss the potential of current pharmacological strategies. Bone loss in space is fuelled by bone resorption. Alendronate, an oral bisphosphonate, reduced bone losses in experimental bed rest and space. However, gastrointestinal side effects precluded its further utilization in space. Zoledronate (a potent bisphosphonate), denosumab (RANKL antagonist) and romosozumab (sclerostin antagonist) are all administered via injection. They effectively suppress bone resorption and are routinely prescribed against osteoporosis. Their serious adverse effects, namely, osteonecrosis of the jaw and atypical femur fractures occur very rarely when the usage is limited to 1 or 2 years. Hence, utilization of one of these compounds may outweigh the bone risks of space travelling, in particular in those with high bone resorption rates. Muscle wasting in space is likely due to hampered muscle protein synthesis. Even though this might theoretically be countered by the synthesis-boosting effects of anabolic steroids, the practical grounds for such recommendation are currently weak. Moreover, they reveal their full potential only when combined with an anabolic exercise stimulus, for example, via strength training. It therefore seems that a combination of exercise and pharmacological countermeasures should be considered for musculoskeletal health on the way to the Moon and Mars and back.
PubMed: 37559171
DOI: 10.1111/bcp.15877 -
Materials (Basel, Switzerland) Jun 2024The surface modification of dental implants plays an important role in establishing a successful interaction of the implant with the surrounding tissue, as the...
The surface modification of dental implants plays an important role in establishing a successful interaction of the implant with the surrounding tissue, as the bioactivity and osseointegration properties are strongly dependent on the physicochemical properties of the implant surface. A surface coating with bioactive molecules that stimulate the formation of a mineral calcium phosphate (CaP) layer has a positive effect on the bone bonding process, as biomineralization is crucial for improving the osseointegration process and rapid bone ingrowth. In this work, the spontaneous deposition of calcium phosphate on the titanium surface covered with chemically stable and covalently bound alendronate molecules was investigated using an integrated experimental and theoretical approach. The initial nucleation of CaP was investigated using quantum chemical calculations at the density functional theory (DFT) level. Negative Gibbs free energies show a spontaneous nucleation of CaP on the biomolecule-covered titanium oxide surface. The deposition of calcium and phosphate ions on the alendronate-modified titanium oxide surface is governed by Ca-phosphonate (-POH) interactions and supported by hydrogen bonding between the phosphate group of CaP and the amino group of the alendronate molecule. The morphological and structural properties of CaP deposit were investigated using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy. This integrated experimental-theoretical study highlights the spontaneous formation of CaP on the alendronate-coated titanium surface, confirming the bioactivity ability of the alendronate coating. The results provide valuable guidance for the promising forthcoming advancements in the development of biomaterials and surface modification of dental implants.
PubMed: 38893965
DOI: 10.3390/ma17112703 -
Frontiers in Immunology 2023Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure...
Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy. Aminobisphosphonates (N-BPs) that include pamidronate, zoledronate, or alendronate, are the first-line treatment of bone-related diseases including osteoporosis and bone malignancies. Here, we show the use of N-BPs as a novel class of LRA: we found in assays using primary cells from ART-suppressed people living with HIV-1 that N-BPs induce HIV-1 from latency to levels that are comparable to the T cell activator phytohemagglutinin (PHA). RNA sequencing and mechanistic data suggested that reactivation may occur through activation of the activator protein 1 signaling pathway. Stored samples from a prior clinical trial aimed at analyzing the effect of alendronate on bone mineral density, provided further evidence of alendronate-mediated latency reversal and activation of immune effector cells. Decay of the reservoir measured by IPDA was however not detected. Our results demonstrate the novel use of N-BPs to reverse HIV-1 latency while inducing immune effector functions. This preliminary evidence merits further investigation in a controlled clinical setting possibly in combination with therapeutic vaccination.
Topics: Humans; HIV Infections; HIV-1; Virus Activation; Virus Latency; Alendronate; HIV Seropositivity
PubMed: 37744358
DOI: 10.3389/fimmu.2023.1219250 -
Journal of Bone and Mineral Metabolism Nov 2023To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks.
MATERIALS AND METHODS
Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups.
RESULTS
Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13-0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40-2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study.
CONCLUSION
Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ.
Topics: Humans; Alendronate; Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Diphosphonates; East Asian People; Osteoporosis; Reproducibility of Results; Teriparatide; Tooth Mobility
PubMed: 37897672
DOI: 10.1007/s00774-023-01466-3