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The Journal of the American Academy of... Sep 2015Osteoporosis-related fractures create a heavy economic and healthcare burden. Although diphosphonate medications have been successful at decreasing the risk of... (Review)
Review
Osteoporosis-related fractures create a heavy economic and healthcare burden. Although diphosphonate medications have been successful at decreasing the risk of osteoporotic fragility fractures and have become staples in the treatment of osteoporosis, concerns have been raised about the association of diphosphonate therapy with spontaneous nonvertebral fractures. Diphosphonate fractures are characteristically transverse or slightly oblique in nature and occur in the lateral cortex, or tension side, of the subtrochanteric region of the femur where diffuse cortical thickening and fracture can be observed on radiographs. A multidisciplinary approach incorporating both medical and surgical teams should be used in the case of diphosphonate-associated fractures. Future medical and surgical developments that augment fracture fixation and counteract diphosphonate-associated osteoclast apoptosis may play a role in therapy. Although diphosphonate use has decreased the rate of osteoporosis-related fractures, increased awareness and association with atypical subtrochanteric fractures is an important concern for clinicians to keep in mind.
Topics: Bone Density Conservation Agents; Diphosphonates; Femoral Fractures; Fracture Fixation; Humans; Osteoporosis; Patient Care Team
PubMed: 26195566
DOI: 10.5435/JAAOS-D-14-00024 -
Tidsskrift For Den Norske Laegeforening... Aug 2007
Review
Topics: Aged; Alendronate; Bone Density Conservation Agents; Dental Care; Diphosphonates; Female; Humans; Jaw Diseases; Male; Middle Aged; Osteonecrosis; Osteoporosis; Osteoporosis, Postmenopausal; Patient Education as Topic; Risk Factors
PubMed: 17700737
DOI: No ID Found -
European Journal of Nuclear Medicine 1982The bone scan is generally recognized to be an extremely powerful investigational tool in the evaluation of patients with skeletal disease. Currently 99mTc-methylene...
The bone scan is generally recognized to be an extremely powerful investigational tool in the evaluation of patients with skeletal disease. Currently 99mTc-methylene diphosphonate is the most widely used bone scanning agent, but recently several new diphosphonate compounds have been introduced which appear to have relatively higher skeletal affinity, leading to greater absolute uptake of tracer by bone. While the resulting improved contrast between bone and background soft-tissue may provide more pleasing scan images, it is not clear that increased bone uptake of tracer is equally desirable for identification of disease. Nevertheless, to date, no significant difference in lesion detection has been found in any comparative study of diphosphonate compounds. In this review the clinical studies evaluating diphosphonate bone scanning agents are summarized and the properties required of an ideal bone scanning agent in both benign and malignant disease discussed.
Topics: Bone Diseases; Bone Neoplasms; Diphosphonates; Etidronic Acid; Humans; Organotechnetium Compounds; Radionuclide Imaging; Technetium; Technetium Tc 99m Medronate
PubMed: 6217074
DOI: 10.1007/BF00257217 -
Maturitas Aug 2002
Review
Topics: Alendronate; Diphosphonates; Drug Administration Schedule; Estrogen Replacement Therapy; Etidronic Acid; Female; Humans; Osteoporosis, Postmenopausal; Risedronic Acid
PubMed: 12361885
DOI: 10.1016/s0378-5122(02)00145-7 -
Seminars in Nuclear Medicine Nov 2009Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The... (Review)
Review
Quantitative bone scan imaging has a useful role in research for examining the pathophysiology of metabolic bone diseases and the response of patients to treatment. The advantage of nuclear medicine imaging as a way of measuring the rate of bone remodeling is that either the whole skeleton or discrete regions of interest (ROIs) may be studied depending on whether there is diffuse or localized disease. This article reviews methods of quantifying (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) kinetics based on a standard bone scan examination by measuring the plasma clearance of tracer to the whole skeleton and/or selected ROIs drawn on the bone scan image. Although the measurement of bone plasma clearance requires blood sampling to find the input curve for free (eg, nonprotein bound) (99m)Tc-MDP, we argue that plasma clearance studies give a more physiological approach in a better accord with the underlying changes in bone turnover than conventional measurements of whole-body retention or bone uptake. We describe 3 methods of measuring whole-skeleton (99m)Tc-MDP plasma clearance (K(bone)): (1) the area under the curve (AUC) method based on taking 6 blood samples at 5, 15, 60, 120, 180, and 240 minutes and measuring the plasma concentration of free (99m)Tc-MDP by ultrafiltration using a 30-kDa filter. The AUC method requires a simultaneous measurement of glomerular filtration rate using (51)Cr-EDTA as a cotracer; (2) the modified Brenner method, which measures K(bone) by drawing a soft-tissue ROI over the adductor muscles and plotting the soft tissue counts at 1, 2, 3, and 4 hours against the AUC values at the corresponding time points; (3) the Patlak method based on combining gamma camera measurements of whole-body retention with plasma data and measuring K(bone) from the slope of the Patlak plot fitted to the 2, 3, and 4 hours data points. Unlike the first 2 methods, the Patlak plot can also be used to measure regional values of K(bone) for any chosen ROI. Initial studies have shown good agreement between the 3 methods of measuring K(bone), and highly significant correlations between the change in K(bone) values during treatment and the corresponding changes in serum and urinary measurements of biochemical markers of bone formation and bone resorption.
Topics: Animals; Area Under Curve; Bone and Bones; Diphosphonates; Humans; Metabolic Clearance Rate; Models, Biological; Organotechnetium Compounds; Radionuclide Imaging; Ultrafiltration
PubMed: 19801217
DOI: 10.1053/j.semnuclmed.2009.05.001 -
Implant Dentistry Aug 2013The aim of this study was to promote the immobilization of a bone activity biomodulator (diphosphonate) on titanium, commonly used in implant dentistry, to provide a...
PURPOSE
The aim of this study was to promote the immobilization of a bone activity biomodulator (diphosphonate) on titanium, commonly used in implant dentistry, to provide a local method of delivering this drug during the osseointegration process.
METHODS
The implant material used in this study was commercially wrought titanium (Ticp), 99.9 mass%, grade II. From this material, discs of 15 mm diameter and 1 mm thick were fabricated. These discs underwent 3 sequential surface modification processes: (a) acid-etching, (b) hydroxyapatite coating, and (c) immersion in disodium pamidronate solution. Scanning electron microscopy, X-ray fluorescence, and X-ray diffraction analyses were carried out to characterize the surface created.
RESULTS
The results of these analyses demonstrate that the acid-etching process, followed by the sintering of hydroxyapatite particles and immersion in a solution of disodium pamidronate were effective for diphosphonate immobilization on the titanium surface.
CONCLUSIONS
The methodology used in this study allows us to conclude that immersion of hydroxyapatite-coated titanium in a solution of diphosphonate was efficient to promote the immobilization of this drug on the titanium surface.
Topics: Acid Etching, Dental; Bone Density Conservation Agents; Coated Materials, Biocompatible; Crystallography; Dental Materials; Diphosphonates; Drug Delivery Systems; Durapatite; Humans; Hydrofluoric Acid; Materials Testing; Microscopy, Electron, Scanning; Nitric Acid; Osseointegration; Pamidronate; Spectrometry, X-Ray Emission; Surface Properties; Titanium; X-Ray Diffraction
PubMed: 23736311
DOI: 10.1097/ID.0b013e31828edd13 -
Bone Jul 2011
Topics: Calcification, Physiologic; Diphosphonates; Humans
PubMed: 21665184
DOI: 10.1016/j.bone.2011.05.019 -
Molecules (Basel, Switzerland) Apr 2022All the enantiomers of (1-amino-3-hydroxypropane-1,3-diyl)diphosphonic acid, newly design phosphonate analogues of 4-hydroxyglutamic acids, were obtained. The synthetic...
All the enantiomers of (1-amino-3-hydroxypropane-1,3-diyl)diphosphonic acid, newly design phosphonate analogues of 4-hydroxyglutamic acids, were obtained. The synthetic strategy involved Abramov reactions of diethyl ()- and ()-1-(-Boc-amino)-3-oxopropylphosphonates with diethyl phosphite, separation of diastereoisomeric [1-(-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates as -protected esters, followed by their hydrolysis to the enantiomeric phosphonic acids. The absolute configuration of the enantiomeric phosphonates was established by comparing the P NMR chemical shifts of respective ()--methylmandelic acid esters obtained from respective pairs of - and -[1-(-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates according to the Spilling rule.
Topics: Diphosphonates; Esters; Glutamates; Organophosphonates; Stereoisomerism
PubMed: 35566049
DOI: 10.3390/molecules27092699 -
Bioorganic & Medicinal Chemistry Letters Aug 2021The G-coupled P2Y receptor (P2YR) is a component of the purinergic signaling system and functions in inflammatory, cardiovascular and metabolic processes. UDP, the...
The G-coupled P2Y receptor (P2YR) is a component of the purinergic signaling system and functions in inflammatory, cardiovascular and metabolic processes. UDP, the native P2YR agonist and P2YR partial agonist, is subject to hydrolysis by ectonucleotidases. Therefore, we have synthesized UDP/CDP analogues containing a stabilizing α,β-methylene bridge as P2YR agonists and identified compatible affinity-enhancing pyrimidine modifications. A distal binding region on the receptor was explored with 4-benzyloxyimino cytidine 5'-diphosphate analogues and their potency determined in a calcium mobilization assay. A 4-trifluoromethyl-benzyloxyimino substituent in 25 provided the highest human P2YR potency (MRS4554, 0.57 µM), and a 5-fluoro substitution of the cytosine ring in 28 similarly enhanced potency, with >175- and 39-fold selectivity over human P2YR, respectively. However, 3-alkyl (31-33, 37, 38), β-d-arabinofuranose (39) and 6-aza (40) substitution prevented P2YR activation. Thus, we have identified new α,β-methylene bridged N-extended CDP analogues as P2YR agonists that are highly selective over the P2YR.
Topics: Diphosphonates; Dose-Response Relationship, Drug; Humans; Molecular Structure; Pyrimidine Nucleotides; Receptors, Purinergic P2; Structure-Activity Relationship
PubMed: 34048882
DOI: 10.1016/j.bmcl.2021.128137 -
The Journal of the American Academy of... 2003
Review
Topics: Bone Diseases, Metabolic; Bone Neoplasms; Costs and Cost Analysis; Diphosphonates; Drug Interactions; Humans
PubMed: 12699366
DOI: 10.5435/00124635-200301000-00001