-
Archives of Osteoporosis Mar 2024This retrospective study compared the efficacy of anabolic agents (romosozumab and teriparatide) with that of alendronate in preventing subsequent vertebral body...
UNLABELLED
This retrospective study compared the efficacy of anabolic agents (romosozumab and teriparatide) with that of alendronate in preventing subsequent vertebral body fractures (SVBFs) after balloon kyphoplasty (BKP). All anabolic agents significantly reduced SVBFs. Romosozumab was most effective in increasing bone mineral density (BMD) and completely suppressed distant vertebral body fractures.
INTRODUCTION
To determine optimal anti-osteoporosis medications, we compared romosozumab and teriparatide to alendronate as a control from perioperative BKP to the 1st postoperative year for treatment and secondary fracture prevention in osteoporosis.
METHODS
A total of 603 patients who underwent initial BKP for osteoporotic vertebral fractures were evaluated and categorized into five groups based on drug administration: romosozumab (group R, 155 patients), twice-weekly teriparatide (group TW, 48), weekly teriparatide (group W, 151), daily teriparatide (group D, 138), and alendronate (control) (group C, 111). The 1-year incidence of SVBFs, BMD change rate, and probability of requiring BKP were compared among the groups.
RESULTS
SVBF incidence was 3.9%, 6.5%, 8.3%, 6.0%, and 14.4% in groups R, D, TW, W, and C, respectively, with all other groups exhibiting significantly lower rates than group C. The groups that administered the anabolic agents had a notably lower incidence of distant fractures than group C. Compared with group C, group R showed significantly higher BMD change rates in lumbar vertebral bodies at 4, 8, and 12 months and group D at 12 months. Anabolic agent groups exhibited significantly higher improvement rates than group C after conservative treatment alone.
CONCLUSION
The anabolic agents were found to be more effective at reducing the incidence of SVBF (especially distant vertebral fractures) than alendronate. These agents decreased the rate of repeat BKP even after the occurrence of a fracture. Overall, the use of an anabolic agent for the treatment of osteoporosis after BKP is better than the use of alendronate, even when treatment is initiated in the perioperative stage.
Topics: Humans; Vertebral Body; Kyphoplasty; Teriparatide; Alendronate; Retrospective Studies; Anabolic Agents; Osteoporosis; Osteoporotic Fractures; Bone Density; Spinal Fractures; Fractures, Compression; Bone Density Conservation Agents
PubMed: 38512565
DOI: 10.1007/s11657-024-01374-7 -
Biological & Pharmaceutical Bulletin 2024Osteoporosis is caused by imbalance between osteogenesis and bone resorption, thus, osteogenic drugs and resorption inhibitors are used for treatment of osteoporosis....
Osteoporosis is caused by imbalance between osteogenesis and bone resorption, thus, osteogenic drugs and resorption inhibitors are used for treatment of osteoporosis. The present study examined the effects of (R)-4-(1-hydroxyethyl)-3-{4-[2-(tetrahydropyran-4-yloxy)ethoxy]phenoxy}benzamide (KY-273), a diphenyl ether derivative, on CDK8/19 activity, osteoblast differentiation and femoral bone using micro-computed tomography in female rats. KY-273 potently inhibited CDK8/19 activity, promoted osteoblast differentiation with an increase in alkaline phosphatase (ALP) activity, and gene expression of type I collagen, ALP and BMP-4 in mesenchymal stem cells (ST2 cells). In female rat femur, ovariectomy decreased metaphyseal trabecular bone volume (Tb.BV), mineral content (Tb.BMC), yet had no effect on metaphyseal and diaphyseal cortical bone volume (Ct.BV), mineral content (Ct.BMC) and strength parameters (BSPs). In ovaries-intact and ovariectomized rats, oral administration of KY-273 (10 mg/kg/d) for 6 weeks increased metaphyseal and diaphyseal Ct.BV, Ct.BMC, and BSPs without affecting medullary volume (Med.V), but did not affect Tb.BV and Tb.BMC. In ovariectomized rats, alendronate (3 mg/kg/d) caused marked restoration of Tb.BV, Tb.BMC and structural parameters after ovariectomy, and increased metaphyseal but not diaphyseal Ct.BV, Ct.BMC, and BSPs. In ovaries-intact and ovariectomized rats, by the last week, KY-273 increased bone formation rate/bone surface at the periosteal but not the endocortical side. These findings indicate that KY-273 causes osteogenesis in cortical bone at the periosteal side without reducing Med.V. In conclusion, KY-273 has cortical-bone-selective osteogenic effects by osteoblastogenesis via CDK8/19 inhibition in ovaries-intact and ovariectomized rats, and is an orally active drug candidate for bone diseases such as osteoporosis in monotherapy and combination therapy.
Topics: Humans; Rats; Female; Animals; Osteogenesis; Bone Density; Rats, Sprague-Dawley; X-Ray Microtomography; Osteoporosis; Ovariectomy; Mesenchymal Stem Cells; Minerals; Cyclin-Dependent Kinase 8
PubMed: 38508765
DOI: 10.1248/bpb.b23-00834 -
Immunology Letters Jun 2024Bacillus Calmette-Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called trained immunity mediated by... (Randomized Controlled Trial)
Randomized Controlled Trial
Bacillus Calmette-Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called trained immunity mediated by epigenetic and metabolic reprogramming. Cholesterol synthesis plays an amplifying role in trained immunity through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis. We explored their effects on trained immunity induced by BCG in a placebo-controlled clinical study (NL74082.091.20) in young, healthy individuals. Participants receiving single-dose oral alendronate on the day of BCG vaccination had more neutrophils and plasma cells one month after treatment. Alendronate led to reduced proinflammatory cytokine production by PBMCs stimulated with heterologous bacterial and viral stimuli one month later. Furthermore, the addition of alendronate transcriptionally suppressed multiple immune response pathways in PBMCs upon stimulation. Our findings indicate that N-BPs modulate the long-lasting effects of BCG vaccination on the cytokine production capacity of innate immune cells.
Topics: Humans; BCG Vaccine; Cytokines; Alendronate; Male; Adult; Female; Young Adult; Vaccination; Leukocytes, Mononuclear; Immunity, Innate; Healthy Volunteers; Immunologic Memory
PubMed: 38479480
DOI: 10.1016/j.imlet.2024.106851 -
Journal of Bone and Mineral Research :... May 2024Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce... (Randomized Controlled Trial)
Randomized Controlled Trial
Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce fracture risk within 1 yr. DXA-based 3D modeling of the hip was used to assess estimated changes in cortical and trabecular bone parameters and map the distribution of 3D changes in bone parameters over time in patients from 2 randomized controlled clinical trials: FRAME (romosozumab vs placebo followed by denosumab) and ARCH (romosozumab vs alendronate followed by alendronate). For each study, data from a subset of ~200 women per treatment group who had TH DXA scans at baseline and months 12 and 24 and had provided consent for future research were analyzed post hoc. 3D-SHAPER software v2.11 (3D-SHAPER Medical) was used to generate patient-specific 3D models from TH DXA scans. Percentage changes from baseline to months 12 and 24 in areal BMD (aBMD), integral volumetric BMD (vBMD), cortical thickness, cortical vBMD, cortical surface BMD (sBMD), and trabecular vBMD were evaluated. Data from 377 women from FRAME (placebo, 190; romosozumab, 187) and 368 women from ARCH (alendronate, 185; romosozumab, 183) with evaluable 3D assessments at baseline and months 12 and 24 were analyzed. At month 12, treatment with romosozumab vs placebo in FRAME and romosozumab vs alendronate in ARCH resulted in greater increases in aBMD, integral vBMD, cortical thickness, cortical vBMD, cortical sBMD, and trabecular vBMD (P < .05 for all). At month 24, cumulative gains in all parameters were greater in the romosozumab-to-denosumab vs placebo-to-denosumab sequence and romosozumab-to-alendronate vs alendronate-to-alendronate sequence (P < .05 for all). 3D-SHAPER analysis provides a novel technique for estimating changes in cortical and trabecular parameters from standard hip DXA images. These data add to the accumulating evidence that romosozumab improves hip bone density and structure, thereby contributing to the antifracture efficacy of the drug.
Topics: Humans; Alendronate; Female; Denosumab; Absorptiometry, Photon; Bone Density; Aged; Antibodies, Monoclonal; Imaging, Three-Dimensional; Middle Aged; Hip
PubMed: 38477808
DOI: 10.1093/jbmr/zjae028 -
Journal of Bone and Mineral Research :... May 2024Bone histomorphometric endpoints in transilial biopsies may be associated with an increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who...
Bone histomorphometric endpoints in transilial biopsies may be associated with an increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BPs). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time-matched patients who either had AFF or did not have AFF. In this study, we performed transiliac bone biopsies in 52 White postmenopausal women with (n = 20) and without (n = 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4-17 yr. Despite the matched range of treatment duration (4-17 yr), AFF patients received alendronate for significantly longer time (10.7 yr) than non-AFF patients (8.0 yr) (P = .014). Bone histomorphometric endpoints reflecting microstructure and turnover were assessed in cancellous, intracortical, and endocortical envelopes from transilial biopsy specimens obtained from BP-treated patients 3-6 mo after AFF and from non-AFF patients with similar age-, gender-, and range of BP treatment duration. However, in both cancellous and intracortical envelopes, AFF patients had significantly lower wall thickness (W.Th) and higher osteoclast surface (Oc.S/BS) than non-AFF patients. In addition, AFF patients had significantly higher eroded surface (ES/BS) only in the intracortical envelope. None of the dynamic variables related to bone formation and turnover differed significantly between the groups. In conclusion, in the ilium of BP-treated patients with osteoporosis, AFF patients have lower thickness of superficial bone (lower W.Th) of the cancellous and cortical envelopes than non-AFF patients. AFF and non-AFF patients have a similar bone turnover rate in the ilium. Furthermore, in this population, as in previous work, AFF is more likely to occur in BP-treated patients with longer treatment duration.
Topics: Humans; Female; Femoral Fractures; Aged; Postmenopause; Middle Aged; Diphosphonates; Alendronate; White
PubMed: 38477744
DOI: 10.1093/jbmr/zjae018 -
European Journal of Medicinal Chemistry Apr 2024The antitumoral activity of hydroxymethylene bisphosphonates (HMBP) such as alendronate or zoledronate is hampered by their exceptional bone-binding properties and their...
The antitumoral activity of hydroxymethylene bisphosphonates (HMBP) such as alendronate or zoledronate is hampered by their exceptional bone-binding properties and their short plasmatic half-life which preclude their accumulation in non-skeletal tumors. In this context, the use of lipophilic prodrugs represents a simple and straightforward strategy to enhance the biodistribution of bisphosphonates in these tissues. We describe in this article the synthesis of light-responsive prodrugs of HMBP alendronate. These prodrugs include lipophilic photo-removable nitroveratryl groups which partially mask the highly polar alendronate HMBP scaffold. Photo-responsive prodrugs of alendronate are stable in physiological conditions and display reduced toxicity compared to alendronate against MDA-MB-231 cancer cells. However, the antiproliferative effect of these prodrugs is efficiently restored after cleavage of their nitroveratryl groups upon exposure to UV light. In addition, substitution of alendronate with such photo-responsive substituents drastically reduces its bone-binding properties, thereby potentially improving its biodistribution in soft tissues after i.v. administration. The development of such lipophilic photo-responsive prodrugs is a promising approach to fully exploit the anticancer effect of HMBPs on non-skeletal tumors.
Topics: Humans; Alendronate; Prodrugs; Tissue Distribution; Diphosphonates; Neoplasms
PubMed: 38460269
DOI: 10.1016/j.ejmech.2024.116307 -
BMC Pediatrics Mar 2024Fanconi-Bickel syndrome is characterized by hepatorenal disease caused by anomalous glycogen storage. It occurs due to variants in the SLC2A2 gene. We present a male...
BACKGROUND
Fanconi-Bickel syndrome is characterized by hepatorenal disease caused by anomalous glycogen storage. It occurs due to variants in the SLC2A2 gene. We present a male patient of 2 years 7 months old, with failure to thrive, hepatomegaly, metabolic acidosis, hypophosphatemia, hypokalemia, hyperlactatemia.
RESULTS
Exome sequencing identified the homozygous pathogenic variant NM_000340.2(SLC2A2):c.1093 C > T (p.Arg365Ter), related with Fanconi-Bickel syndrome. He received treatment with bicarbonate, amlodipine, sodium citrate and citric acid solution, enalapril, alendronate and zolendronate, and nutritional management with uncooked cornstarch, resulting in an improvement of one standard deviation in weight and height.
CONCLUSIONS
The importance of knowing the etiology in rare genetic disease is essential, not only to determine individual and familial recurrence risk, but also to establish the treatment and prognosis; in this sense, access to a new genomic technology in low- and middle-income countries is essential to shorten the diagnostic odyssey.
Topics: Humans; Male; Fanconi Syndrome; High-Throughput Nucleotide Sequencing; Homozygote; Prognosis; Child, Preschool
PubMed: 38454379
DOI: 10.1186/s12887-024-04641-1 -
Radiology Case Reports May 2024Paget's disease of bone is a disorder of osteoclasts which hampers the physiological process of bone remodeling. It is the most common metabolic orthopedic disease in...
Paget's disease of bone is a disorder of osteoclasts which hampers the physiological process of bone remodeling. It is the most common metabolic orthopedic disease in the Caucasian populace; we report the diagnosis of Paget's disease of bone in a South-Asian male in his early 50s with a history of gastrointestinal symptoms, weight loss and back pain. An alkaline phosphatase level of 1104 IU/L was noted. A 3-phase bone scan showed noncontiguous heterogenous nuclear uptake. After exhaustive evaluation, the patient was diagnosed with Paget's disease of bone. Despite the disease activity being mitigated by alendronate and monitored by ALP levels within normal range per protocol, the patient had compression fractures of the vertebrae requiring early reinitiation of oral bisphosphonates. This raised doubts about the efficacy of metabolic marker-based management in Paget's disease of bone.
PubMed: 38434784
DOI: 10.1016/j.radcr.2024.01.037 -
Hip & Pelvis Mar 2024We report on the case of a 52-year-old female who presented with a stress fracture after undergoing an endoscopic resection of the lesser trochanter in ischiofemoral...
We report on the case of a 52-year-old female who presented with a stress fracture after undergoing an endoscopic resection of the lesser trochanter in ischiofemoral impingement, which was resistant to maximal conservative treatment. To the best of our knowledge, this complication has not been previously described. Non-weight-bearing and intravenous alendronic acid were prescribed for management. No additional surgery was required. The patient was pain free with the ability to perform sports on the same level as before and had no complaints.
PubMed: 38420740
DOI: 10.5371/hp.2024.36.1.70 -
Journal of Feline Medicine and Surgery Feb 2024Cats with ionized hypercalcemia that were fed diets with either more than 200 mg calcium per 100 kilocalories (kcal), a calcium:phosphorus (Ca:P) ratio greater than...
CASE SERIES SUMMARY
Cats with ionized hypercalcemia that were fed diets with either more than 200 mg calcium per 100 kilocalories (kcal), a calcium:phosphorus (Ca:P) ratio greater than 1.4:1 or both, based on diet history, were included in this case series. Ionized hypercalcemia was documented at least twice in all cats before enrollment. Cats were referred for evaluation of ionized hypercalcemia (n = 5) or were incidentally found to have ionized hypercalcemia (n = 5). After medical workups, cats were diagnosed with either idiopathic hypercalcemia (IHC; n = 7) or chronic kidney disease (n = 3). Cats receiving medications to treat IHC (eg, alendronate, corticosteroids) were excluded. Nutritional recommendations were made to transition the cats to diets with less thn 200 mg calcium per 100 kcal and a Ca:P ratio less than 1.4:1. Ionized calcium (iCa) concentrations were rechecked in all cats, with a median recheck time of 9 weeks (range 3-20). Of the 10 cats, nine (90%) had a decrease in iCa. Of the 10 cats, six (60%) became normocalcemic after the diet change, three (30%) had a partial response and one (10%) did not respond. Of the four cats that did not achieve normocalcemia with a change in diet, two (50%) received chia seeds (1-2 g per day), and at the next recheck, both cats' iCa concentrations had normalized. Three cats had a long-term follow-up. Ionized normocalcemia was maintained for at least two consecutive follow-up visits over a median follow-up period of 33 weeks (range 12-34).
RELEVANCE AND NOVEL INFORMATION
Dietary calcium concentrations and the dietary Ca:P ratio appear to be important variables in considering nutritional approaches for hypercalcemic cats.
Topics: Cats; Animals; Hypercalcemia; Calcium; Renal Insufficiency, Chronic; Alendronate; Cat Diseases
PubMed: 38415620
DOI: 10.1177/1098612X241229811