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Journal of Bone and Mineral Research :... Nov 2022Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains... (Meta-Analysis)
Meta-Analysis
The Efficacy and Safety of Medical and Surgical Therapy in Patients With Primary Hyperparathyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Both medical and surgical therapy represent potential management options for patients with asymptomatic primary hyperparathyroidism (PHPT). Because uncertainty remains regarding both medical and surgical therapy, this systematic review addresses the efficacy and safety of medical therapy in asymptomatic patients or symptomatic patients who decline surgery and surgery in asymptomatic patients. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, and PubMed from inception to December 2020, and included randomized controlled trials in patients with PHPT that compared nonsurgical management with medical therapy versus without medical therapy and surgery versus no surgery in patients with asymptomatic PHPT. For surgical complications we included observational studies. Paired reviewers addressed eligibility, assessed risk of bias, and abstracted data for patient-important outcomes. We conducted random-effects meta-analyses to pool relative risks and mean differences with 95% confidence intervals and used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess quality of evidence for each outcome. For medical therapy, 11 trials reported in 12 publications including 438 patients proved eligible: three addressed alendronate, one denosumab, three cinacalcet, two vitamin D, and two estrogen therapy. Alendronate, denosumab, vitamin D, and estrogen therapy all increased bone density. Cinacalcet probably reduced serum calcium and parathyroid hormone (PTH) levels. Cinacalcet and vitamin D may have a small or no increase in overall adverse events. Very-low-quality evidence raised the possibility of an increase in serious adverse events with alendronate and denosumab. The trials also provided low-quality evidence for increased bleeding and mastalgia with estrogen therapy. For surgery, six trials presented in 12 reports including 441 patients proved eligible. Surgery achieved biochemical cure in 96.1% (high quality). We found no convincing evidence supporting an impact of surgery on fracture, quality of life, occurrence of kidney stones, and renal function, but the evidence proved low or very low quality. Surgery was associated with an increase in bone mineral density. For patients with symptomatic and asymptomatic PHPT, who are not candidates for parathyroid surgery, cinacalcet probably reduced serum calcium and PTH levels; anti-resorptives increased bone density. For patients with asymptomatic PHPT, surgery usually achieves biochemical cure. These results can help to inform patients and clinicians regarding use of medical therapy and surgery in PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Cinacalcet; Hyperparathyroidism, Primary; Alendronate; Calcium; Quality of Life; Denosumab; Randomized Controlled Trials as Topic; Parathyroid Hormone; Vitamin D; Estrogens
PubMed: 36053960
DOI: 10.1002/jbmr.4685 -
Experimental Neurobiology Feb 2022Spinal cord injury is a destructive disease characterized by motor/sensory dysfunction and severe inflammation. Alendronate is an anti-inflammatory molecule and may...
Spinal cord injury is a destructive disease characterized by motor/sensory dysfunction and severe inflammation. Alendronate is an anti-inflammatory molecule and may therefore be of benefit in the treatment of the inflammation associated with spinal cord injury. This study aimed to evaluate whether alendronate attenuates motor/sensory dysfunction and the inflammatory response in a thoracic spinal cord clip injury model. Alendronate was intraperitoneally administered at 1 mg/kg/day or 5 mg/kg/day from day (D) 0 to 28 post-injury (PI). The histopathological evaluation showed an alleviation of the inflammatory response, including the infiltration of inflammatory cells, and a decrease in gliosis. Alendronate also led to reductions in the levels of inflammation-related molecules, including mitogen-activated protein kinase, p53, pro-inflammatory cytokines, and pro-inflammatory mediators. Neuro-behavioral assessments, including the Basso, Beattie, and Bresnahan scale for locomotor function, the von Frey filament test, the hot plate test, and the cold stimulation test for sensory function, and the horizontal ladder test for sensorimotor function improved significantly in the alendronate-treated group at D28PI. Taken together, these results suggest that alendronate treatment can inhibit the inflammatory response in spinal cord injury thus improving functional responses.
PubMed: 35256544
DOI: 10.5607/en21030 -
Frontiers in Cell and Developmental... 2021Bisphosphonates are drugs widely used to reduce bone resorption, increase bone mineral density and control age-related bone loss. Although there are studies reporting...
BACKGROUND
Bisphosphonates are drugs widely used to reduce bone resorption, increase bone mineral density and control age-related bone loss. Although there are studies reporting differences in bone structure between young and old adults, it is still difficult to predict changes related to bone aging. The aim of this study was to evaluate the effect of age and sodium alendronate on bone repair of femoral fractures in rats.
METHODS
rats ( = 40) were allocated into groups: O (control old-rats), Y (control young-rats), OA (alendronate old-rats) and YA (alendronate young-rats). All animals underwent linear fracture surgery followed by fixation. Groups OA and YA received 1 mg/kg alendronate three times a week until euthanasia. Biochemical analysis of calcium and alkaline phosphatase was done. After euthanasia, femurs were evaluated in relation to cross-section and flexural strength, with three-point bending test. Data were submitted to statistical analysis with significance level of 0.05.
RESULTS
There was no difference in calcium and alkaline phosphatase levels ( > 0.05). Young animals presented lower cross-section than older animals ( < 0.05). Only fractured side, young animals presented major flexural strength than older animals ( < 0.05). There was no difference between the animals that used or not alendronate in relation to cross-section and flexural strength ( > 0.05). When compared fractured and non-fractured femurs, major cross-section on fractured side was observed ( < 0.05). Flexural strength presented higher values in femurs on non-fractured side ( < 0.05). There was correlation of weight and cross-section ( = +0.91) and weight with flexural strength of fractured and non-fractured side, respectively ( = -0.97 and -0.71).
CONCLUSION
In short, there was no difference of calcium and alkaline phosphatase during the bone repair process. Age has influence in cross-section and flexural strength. Alendronate showed no association with these factors.
PubMed: 34026748
DOI: 10.3389/fcell.2021.558285 -
Systematic Reviews Mar 2023To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and... (Meta-Analysis)
Meta-Analysis
Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools.
BACKGROUND
To inform recommendations by the Canadian Task Force on Preventive Health Care, we reviewed evidence on the benefits, harms, and acceptability of screening and treatment, and on the accuracy of risk prediction tools for the primary prevention of fragility fractures among adults aged 40 years and older in primary care.
METHODS
For screening effectiveness, accuracy of risk prediction tools, and treatment benefits, our search methods involved integrating studies published up to 2016 from an existing systematic review. Then, to locate more recent studies and any evidence relating to acceptability and treatment harms, we searched online databases (2016 to April 4, 2022 [screening] or to June 1, 2021 [predictive accuracy]; 1995 to June 1, 2021, for acceptability; 2016 to March 2, 2020, for treatment benefits; 2015 to June 24, 2020, for treatment harms), trial registries and gray literature, and hand-searched reviews, guidelines, and the included studies. Two reviewers selected studies, extracted results, and appraised risk of bias, with disagreements resolved by consensus or a third reviewer. The overview of reviews on treatment harms relied on one reviewer, with verification of data by another reviewer to correct errors and omissions. When appropriate, study results were pooled using random effects meta-analysis; otherwise, findings were described narratively. Evidence certainty was rated according to the GRADE approach.
RESULTS
We included 4 randomized controlled trials (RCTs) and 1 controlled clinical trial (CCT) for the benefits and harms of screening, 1 RCT for comparative benefits and harms of different screening strategies, 32 validation cohort studies for the calibration of risk prediction tools (26 of these reporting on the Fracture Risk Assessment Tool without [i.e., clinical FRAX], or with the inclusion of bone mineral density (BMD) results [i.e., FRAX + BMD]), 27 RCTs for the benefits of treatment, 10 systematic reviews for the harms of treatment, and 12 studies for the acceptability of screening or initiating treatment. In females aged 65 years and older who are willing to independently complete a mailed fracture risk questionnaire (referred to as "selected population"), 2-step screening using a risk assessment tool with or without measurement of BMD probably (moderate certainty) reduces the risk of hip fractures (3 RCTs and 1 CCT, n = 43,736, absolute risk reduction [ARD] = 6.2 fewer in 1000, 95% CI 9.0-2.8 fewer, number needed to screen [NNS] = 161) and clinical fragility fractures (3 RCTs, n = 42,009, ARD = 5.9 fewer in 1000, 95% CI 10.9-0.8 fewer, NNS = 169). It probably does not reduce all-cause mortality (2 RCTs and 1 CCT, n = 26,511, ARD = no difference in 1000, 95% CI 7.1 fewer to 5.3 more) and may (low certainty) not affect health-related quality of life. Benefits for fracture outcomes were not replicated in an offer-to-screen population where the rate of response to mailed screening questionnaires was low. For females aged 68-80 years, population screening may not reduce the risk of hip fractures (1 RCT, n = 34,229, ARD = 0.3 fewer in 1000, 95% CI 4.2 fewer to 3.9 more) or clinical fragility fractures (1 RCT, n = 34,229, ARD = 1.0 fewer in 1000, 95% CI 8.0 fewer to 6.0 more) over 5 years of follow-up. The evidence for serious adverse events among all patients and for all outcomes among males and younger females (<65 years) is very uncertain. We defined overdiagnosis as the identification of high risk in individuals who, if not screened, would never have known that they were at risk and would never have experienced a fragility fracture. This was not directly reported in any of the trials. Estimates using data available in the trials suggest that among "selected" females offered screening, 12% of those meeting age-specific treatment thresholds based on clinical FRAX 10-year hip fracture risk, and 19% of those meeting thresholds based on clinical FRAX 10-year major osteoporotic fracture risk, may be overdiagnosed as being at high risk of fracture. Of those identified as being at high clinical FRAX 10-year hip fracture risk and who were referred for BMD assessment, 24% may be overdiagnosed. One RCT (n = 9268) provided evidence comparing 1-step to 2-step screening among postmenopausal females, but the evidence from this trial was very uncertain. For the calibration of risk prediction tools, evidence from three Canadian studies (n = 67,611) without serious risk of bias concerns indicates that clinical FRAX-Canada may be well calibrated for the 10-year prediction of hip fractures (observed-to-expected fracture ratio [O:E] = 1.13, 95% CI 0.74-1.72, I = 89.2%), and is probably well calibrated for the 10-year prediction of clinical fragility fractures (O:E = 1.10, 95% CI 1.01-1.20, I = 50.4%), both leading to some underestimation of the observed risk. Data from these same studies (n = 61,156) showed that FRAX-Canada with BMD may perform poorly to estimate 10-year hip fracture risk (O:E = 1.31, 95% CI 0.91-2.13, I = 92.7%), but is probably well calibrated for the 10-year prediction of clinical fragility fractures, with some underestimation of the observed risk (O:E 1.16, 95% CI 1.12-1.20, I = 0%). The Canadian Association of Radiologists and Osteoporosis Canada Risk Assessment (CAROC) tool may be well calibrated to predict a category of risk for 10-year clinical fractures (low, moderate, or high risk; 1 study, n = 34,060). The evidence for most other tools was limited, or in the case of FRAX tools calibrated for countries other than Canada, very uncertain due to serious risk of bias concerns and large inconsistency in findings across studies. Postmenopausal females in a primary prevention population defined as <50% prevalence of prior fragility fracture (median 16.9%, range 0 to 48% when reported in the trials) and at risk of fragility fracture, treatment with bisphosphonates as a class (median 2 years, range 1-6 years) probably reduces the risk of clinical fragility fractures (19 RCTs, n = 22,482, ARD = 11.1 fewer in 1000, 95% CI 15.0-6.6 fewer, [number needed to treat for an additional beneficial outcome] NNT = 90), and may reduce the risk of hip fractures (14 RCTs, n = 21,038, ARD = 2.9 fewer in 1000, 95% CI 4.6-0.9 fewer, NNT = 345) and clinical vertebral fractures (11 RCTs, n = 8921, ARD = 10.0 fewer in 1000, 95% CI 14.0-3.9 fewer, NNT = 100); it may not reduce all-cause mortality. There is low certainty evidence of little-to-no reduction in hip fractures with any individual bisphosphonate, but all provided evidence of decreased risk of clinical fragility fractures (moderate certainty for alendronate [NNT=68] and zoledronic acid [NNT=50], low certainty for risedronate [NNT=128]) among postmenopausal females. Evidence for an impact on risk of clinical vertebral fractures is very uncertain for alendronate and risedronate; zoledronic acid may reduce the risk of this outcome (4 RCTs, n = 2367, ARD = 18.7 fewer in 1000, 95% CI 25.6-6.6 fewer, NNT = 54) for postmenopausal females. Denosumab probably reduces the risk of clinical fragility fractures (6 RCTs, n = 9473, ARD = 9.1 fewer in 1000, 95% CI 12.1-5.6 fewer, NNT = 110) and clinical vertebral fractures (4 RCTs, n = 8639, ARD = 16.0 fewer in 1000, 95% CI 18.6-12.1 fewer, NNT=62), but may make little-to-no difference in the risk of hip fractures among postmenopausal females. Denosumab probably makes little-to-no difference in the risk of all-cause mortality or health-related quality of life among postmenopausal females. Evidence in males is limited to two trials (1 zoledronic acid, 1 denosumab); in this population, zoledronic acid may make little-to-no difference in the risk of hip or clinical fragility fractures, and evidence for all-cause mortality is very uncertain. The evidence for treatment with denosumab in males is very uncertain for all fracture outcomes (hip, clinical fragility, clinical vertebral) and all-cause mortality. There is moderate certainty evidence that treatment causes a small number of patients to experience a non-serious adverse event, notably non-serious gastrointestinal events (e.g., abdominal pain, reflux) with alendronate (50 RCTs, n = 22,549, ARD = 16.3 more in 1000, 95% CI 2.4-31.3 more, [number needed to treat for an additional harmful outcome] NNH = 61) but not with risedronate; influenza-like symptoms with zoledronic acid (5 RCTs, n = 10,695, ARD = 142.5 more in 1000, 95% CI 105.5-188.5 more, NNH = 7); and non-serious gastrointestinal adverse events (3 RCTs, n = 8454, ARD = 64.5 more in 1000, 95% CI 26.4-13.3 more, NNH = 16), dermatologic adverse events (3 RCTs, n = 8454, ARD = 15.6 more in 1000, 95% CI 7.6-27.0 more, NNH = 64), and infections (any severity; 4 RCTs, n = 8691, ARD = 1.8 more in 1000, 95% CI 0.1-4.0 more, NNH = 556) with denosumab. For serious adverse events overall and specific to stroke and myocardial infarction, treatment with bisphosphonates probably makes little-to-no difference; evidence for other specific serious harms was less certain or not available. There was low certainty evidence for an increased risk for the rare occurrence of atypical femoral fractures (0.06 to 0.08 more in 1000) and osteonecrosis of the jaw (0.22 more in 1000) with bisphosphonates (most evidence for alendronate). The evidence for these rare outcomes and for rebound fractures with denosumab was very uncertain. Younger (lower risk) females have high willingness to be screened. A minority of postmenopausal females at increased risk for fracture may accept treatment. Further, there is large heterogeneity in the level of risk at which patients may be accepting of initiating treatment, and treatment effects appear to be overestimated.
CONCLUSION
An offer of 2-step screening with risk assessment and BMD measurement to selected postmenopausal females with low prevalence of prior fracture probably results in a small reduction in the risk of clinical fragility fracture and hip fracture compared to no screening. These findings were most applicable to the use of clinical FRAX for risk assessment and were not replicated in the offer-to-screen population where the rate of response to mailed screening questionnaires was low. Limited direct evidence on harms of screening were available; using study data to provide estimates, there may be a moderate degree of overdiagnosis of high risk for fracture to consider. The evidence for younger females and males is very limited. The benefits of screening and treatment need to be weighed against the potential for harm; patient views on the acceptability of treatment are highly variable.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO): CRD42019123767.
Topics: Adult; Female; Humans; Male; Middle Aged; Alendronate; Canada; Denosumab; Diphosphonates; Hip Fractures; Osteoporotic Fractures; Primary Health Care; Primary Prevention; Risedronic Acid; Systematic Reviews as Topic; Zoledronic Acid
PubMed: 36945065
DOI: 10.1186/s13643-023-02181-w -
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 -
Arteriosclerosis, Thrombosis, and... Jul 2019Osteoporosis and cardiovascular diseases are major public health issues. Bone and cardiovascular remodeling share multiple biological markers and pathways. Medical... (Review)
Review
Osteoporosis and cardiovascular diseases are major public health issues. Bone and cardiovascular remodeling share multiple biological markers and pathways. Medical intervention, such as using romosozumab, an antisclerostin antibody, improves the clinical outcome of osteoporosis. However, blocking sclerostin leads to Wnt (wingless/integrated) activation and participation in the cardiovascular remodeling process, which could potentially lead to adverse events. Based on the opposing roles of bisphosphonates and the Wnt pathway on endothelial dysfunction, lipid accumulation and calcification of the vessel walls, the combination of romosozumab and bisphosphonates could be a new therapeutic approach to reducing the risks of adverse cardiovascular events in romosozumab receivers. Visual Overview- An online visual overview is available for this article.
Topics: Adaptor Proteins, Signal Transducing; Alendronate; Antibodies, Monoclonal; Cardiovascular Diseases; Humans; Osteoporosis; Wnt Signaling Pathway
PubMed: 31242037
DOI: 10.1161/ATVBAHA.119.312371 -
Medicina Clinica Oct 2022Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to... (Review)
Review
Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis.
Topics: Alendronate; Bone Density Conservation Agents; Denosumab; Diphosphonates; Female; Humans; Hydroxyapatites; Osteoporosis; Osteoporosis, Postmenopausal; Risedronic Acid; Selective Estrogen Receptor Modulators; Zoledronic Acid
PubMed: 35738929
DOI: 10.1016/j.medcli.2022.04.003 -
Aging Clinical and Experimental Research Nov 2022Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of... (Review)
Review
Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes.
Topics: Humans; Osteoporosis; Diphosphonates; Fractures, Bone; Risedronic Acid; Alendronate
PubMed: 36331798
DOI: 10.1007/s40520-022-02272-z -
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 -
Bone Jul 2022Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new...
Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new bone. Reduced bone formation has been suggested to lead to accumulation of microfractures and contribute to rare side effects in cortical bone such as atypical femur fractures. However, most studies are limited to trabecular bone. In this study, the cortical bone remodeling in human iliac bone specimens of 65 non-treated and 24 alendronate-treated osteoporotic women was investigated using a new histomorphometric classification of intracortical pores. The study showed that only 12.4 ± 11% of the cortical pore area reflected quiescent pores/osteons in alendronate-treated patients versus 8.5 ± 5% in placebo, highlighting that new cortical remodeling events remain to be activated. The percent and size of eroded pores (events in resorption-reversal phase) remained unchanged, but their contribution to total pore area was 1.4-fold higher in alendronate versus placebo treated patients (66 ± 22% vs 48 ± 22%, p < 0.001). On the other hand, the mixed eroded-formative pores (events with mixed resorption-reversal-formation phases) was 2-fold lower in alendronate versus placebo treated patients (19 ± 14% vs 39 ± 23% of total pore area, p < 0.001), and formative pores (event in formation phase) was 2.2-fold lower in alendronate versus placebo treated patients (2.1 ± 2.4% vs 4.6 ± 3.6%, p < 0.01), and their contribution to total pore area was 2.4-fold lower (1.3 ± 2.1% vs 3.1 ± 4.4%, p < 0.05). Importantly, these differences between alendronate and placebo treated patients were significant in patients after 3 years of treatment, not after 2 years of treatment. Collectively, the results support that cortical remodeling events activated during alendronate treatment has a prolonged reversal-resorption phase with a delayed transition to formation, becoming increasingly evident after 3-years of treatment. A potential contributor to atypical femur fractures associated with long-term bisphosphonate treatment.
Topics: Alendronate; Bone Density; Bone Remodeling; Bone and Bones; Cortical Bone; Diphosphonates; Female; Humans
PubMed: 35413490
DOI: 10.1016/j.bone.2022.116419