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Ugeskrift For Laeger Jan 2024Bone turnover markers (BTM) are highly responsive to initiation and changes in anti-osteoporotic therapy. In contrast to the slow treatment-induced changes in bone... (Review)
Review
Bone turnover markers (BTM) are highly responsive to initiation and changes in anti-osteoporotic therapy. In contrast to the slow treatment-induced changes in bone mineral density, the fast changes in BTM enable the clinician to adjust treatment management within a short timeframe. This review describes how BTM can be used for treatment monitoring, including monitoring during discontinuation of alendronate and denosumab therapy. In addition, sources of errors and pitfalls when using BTM monitoring will be described.
Topics: Humans; Bone Density Conservation Agents; Biomarkers; Osteoporosis; Bone Density; Bone Remodeling; Denosumab
PubMed: 38327195
DOI: 10.61409/V07230432 -
Cureus Aug 2023Osteoporosis affects a significant number of postmenopausal women in the United States. Screening is performed using clinical assessments and bone mineral density scans... (Review)
Review
Osteoporosis affects a significant number of postmenopausal women in the United States. Screening is performed using clinical assessments and bone mineral density scans via dual x-ray absorptiometry. Oral therapy is indicated to prevent pathologic fractures in those deemed at increased risk following screening. Bisphosphonates including alendronate, ibandronate, and risedronate are currently first-line oral therapeutics in fracture prevention following the diagnosis of osteoporosis. Hormonal therapies include estrogen-containing therapies, selective estrogen receptor modulators, and other compounds that mimic the effects of estrogen such as tibolone. Lifestyle modifications such as supplementation and physical activity may also contribute to the prevention of osteoporosis and are used as adjuncts to therapy following diagnosis. These therapeutics are limited primarily by their adverse effects. Treatment regimens should be tailored based on significant risk factors demonstrated by patients, adverse effects, and clinical response to treatment. The most severe risk factors relevant to pharmacological selection involve hormone replacement therapies, where concern for venous thrombosis, coronary artery disease, breast, and uterine cancer exist. Bisphosphonates are most commonly associated with gastrointestinal discomfort which may be mitigated with proper administration. Although adverse effects exist, these medications have proven to be efficacious in the prevention of vertebral and non-vertebral fractures in post-menopausal women. Fracture risk should be weighed against the risk of adverse events associated with each of the regimens, with clinical judgment dictating the treatment approach centered around patient goals and experiences.
PubMed: 37664395
DOI: 10.7759/cureus.42870 -
Archives of Endocrinology and Metabolism Nov 2023Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have... (Review)
Review
Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.
Topics: Humans; Female; Diphosphonates; Bone Density Conservation Agents; Quality of Life; Osteoporosis; Alendronate; Zoledronic Acid; Fractures, Bone; Osteoporosis, Postmenopausal
PubMed: 37948565
DOI: 10.20945/2359-4292-2022-0334 -
Osteoporosis International : a Journal... Nov 2023This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with...
UNLABELLED
This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.
PURPOSE
To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting.
METHODS
This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting.
RESULTS
A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab.
CONCLUSIONS
When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab.
Topics: Humans; Female; Aged; Middle Aged; Male; Alendronate; Ibandronic Acid; Zoledronic Acid; Denosumab; Cohort Studies; Bone Density Conservation Agents; Diphosphonates; Osteoporosis; Hip Fractures; Spinal Fractures; Registries; Osteoporosis, Postmenopausal
PubMed: 37493978
DOI: 10.1007/s00198-023-06863-y -
Frontiers in Pharmacology 2024Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian...
Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.
PubMed: 38313307
DOI: 10.3389/fphar.2024.1336075 -
Drug Delivery Dec 2023Low bone mass, degeneration of bone tissue, and disruption of bone microarchitecture are all symptoms of the disease osteoporosis, which can decrease bone strength and...
Low bone mass, degeneration of bone tissue, and disruption of bone microarchitecture are all symptoms of the disease osteoporosis, which can decrease bone strength and increase the risk of fractures. The main objective of the current study was to use a phospholipid-based phase separation gel (PPSG) in combination with an alendronate sodium nanoemulsion (ALS-NE) to help prevent bone resorption in rats. The effect of factors such as concentrations of the ALS aqueous solution, surfactant Plurol Oleique CC 497, and Maisine CC oil on nanoemulsion characteristics such as stability index and globular size was investigated using an l-optimal coordinate exchange statistical design. Injectable PPSG with the best nanoemulsion formulation was tested for viscosity, gel strength, water absorption, and ALS release. ALS retention in the rats' muscles was measured after 30 days. The droplet size and stability index of the optimal nanoemulsion were 90 ± 2.0 nm and 85 ± 1.9%, respectively. When mixed with water, the optimal ALS-NE-loaded PPSG became viscous and achieved 36 seconds of gel strength, which was adequate for an injectable formulation. In comparison with the ALS solution-loaded gel, the newly created optimal ALS-NE-loaded PPSG produced the sustained and regulated release of ALS; hence, a higher percentage of ALS remained in rats' muscles after 30 days. PPSG that has been loaded with an ALS-NE may therefore be a more auspicious, productive, and effective platform for osteoporosis treatment than conventional oral forms.
Topics: Animals; Rats; Alendronate; Emulsions; Osteoporosis; Water
PubMed: 36588399
DOI: 10.1080/10717544.2022.2164094 -
Heliyon Sep 2023Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of...
OBJECTIVES
Bisphosphonates are known to induce a severe adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). Previous studies have proven the impact of bisphosphonates on microperfusion; therefore, this study aimed to investigate alendronate-induced microcirculatory reactions in the calvarial periosteum of rats.
STUDY DESIGN
Bone chambers were implanted into 48 Lewis rats. Microhemodynamics, inflammatory parameters, functional capillary density and defect healing were examined after alendronate treatment for two and six weeks using repetitive intravital fluorescence microscopy for two weeks.
RESULTS
Microhemodynamics remained unchanged. In alendronate-treated rats, inflammation was slightly increased, functional capillary density was significantly reduced (day 10: controls 100.45 ± 5.38 cm/cm, two weeks alendronate treatment 44.77 ± 3.55 cm/cm, six weeks alendronate treatment 27.54 ± 2.23 cm/cm) and defect healing was decelerated. The changes in functional capillary density and defect healing were dose-dependent.
CONCLUSION
The bisphosphonate alendronate has a significant negative impact on periosteal microperfusion in vivo. This could be a promising target for the treatment of MRONJ.
PubMed: 37681156
DOI: 10.1016/j.heliyon.2023.e19468 -
Scientific Reports Jul 2023Atypical femur fracture (AFF) is a rare but catastrophic adverse event first reported in the long-term use of alendronate, one of the most commonly used drugs for...
Atypical femur fracture (AFF) is a rare but catastrophic adverse event first reported in the long-term use of alendronate, one of the most commonly used drugs for osteoporosis currently. However, further evidence is needed to learn more regarding other common anti-osteoporosis drugs and the risk for AFF. In this study, reports of AFF were identified from Food and Drug Administration Adverse Event Reporting System database. Disproportionality analyses were performed to examine the reporting odds ratio (ROR), information component (IC) and adjusted ROR (adj. ROR) signals for AFF for common anti-osteoporosis drugs. A total of 1692 unique AFF reports were identified. The disproportionality signals (the lower bound of 95% confidence interval > 1 for ROR and adjusted ROR, and > 0 for IC) were detected for alendronate, denosumab, pamidronate, risedronate, zoledronate, ibandronate, and teriparatide while no signal was detected for raloxifene, abaloparatide, and romosozumab. When restricted in patients with osteoporosis, the disproportionality signals were still detected for alendronate, pamidronate, risedronate, denosumab, and ibandronate. Our results suggest that alendronate has the largest risk signal, while the risks varied among different bisphosphonates. In addition, denosumab was found statistically associated with AFF in both the entire database and patients with osteoporosis.
Topics: Humans; Alendronate; Bone Density Conservation Agents; Risedronic Acid; Denosumab; Ibandronic Acid; Pharmaceutical Preparations; Pamidronate; Osteoporosis; Diphosphonates; Femur
PubMed: 37407650
DOI: 10.1038/s41598-023-37944-x -
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