pyrophosphate and Osteoporosis

Glucocorticoids remain widely used for many medical conditions, and fractures are the most serious common adverse event related to long-term glucocorticoid use. Glucocorticoid-induced osteoporosis (GIOP) develops in a time- and dose-dependent manner, but even at low doses, an increased risk of fragility fracture may be observed even within the first month of treatment. GIOP is mediated by multiple pathophysiologic mechanisms resulting in an inhibition of bone formation and an increase in bone resorption. The clinical assessment of GIOP has potential pitfalls since dual-energy X-ray absorptiometry (DXA) may underestimate the risk of fracture in patients treated with glucocorticoids. Many national organizations have developed guidelines for assessing fracture risk and treating patients with, or at risk for, GIOP. These groups advocate both antiresorptive agents and bone-forming agents based predominately on their efficacy in improving bone mineral density. Oral bisphosphonates are generally the first-line therapy for GIOP in most patients due to their proven efficacy, good safety, and low cost. For those patients at greater risk of fracture, teriparatide should be considered earlier, based on its ability to significantly reduce vertebral fractures when compared with alendronate. GIOP remains a major public health concern that is at least partially preventable with current and potential future therapeutic options.

Topics: Bone Density Conservation Agents; Calcium; Diphosphates; Glucocorticoids; Hormone Replacement Therapy; Humans; Medication Adherence; Osteoporosis; Vitamin D

We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease.. Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.

Topics: Abnormalities, Multiple; Aortic Diseases; Basal Ganglia Diseases; Calcinosis; Cartilage Diseases; Dental Enamel Hypoplasia; Diphosphates; Enzyme Replacement Therapy; Gaucher Disease; Hand Deformities, Congenital; Humans; Hyperostosis, Cortical, Congenital; Hyperphosphatemia; Interferons; Metacarpus; Muscular Diseases; Odontodysplasia; Osteoporosis; Phosphates; Progeria; Pseudoxanthoma Elasticum; Pulmonary Valve Stenosis; Vascular Calcification

The cardiovascular risk of patients undergoing dialysis is 20-30 times higher than that of individuals of the same age, without abnormal renal function, from the general population. Observational studies of patients with normal and abnormal renal function have shown that there is an association between bone disease, vascular calcification and cardiovascular outcome and that worsening of these conditions happens in parallel. Basic science studies are elucidating several mechanisms that could explain the interaction between bone disease, vascular calcification and cardiovascular outcome. For example, the expression of osteoprotegerin-a protein that regulates bone resorption by binding receptor activator of nuclear factor kappaB (RANK) ligand (RANKL), thus preventing interaction with the receptor RANK and the stimulation of osteoclast maturation-is regulated by several cytokines. Additionally, osteoprotegerin seems involved in the genesis of atherosclerosis. Imbalances of bone mineral metabolism, bone matrix secretion and vascular smooth-muscle-cell apoptosis seem involved in the ossification of the arterial wall in chronic kidney disease, and could explain some of the complex interactions between bone and vascular disease in renal failure. In this article we present a brief review of some of the basic mechanisms involved in vascular calcification and the clinical evidence of an association of vascular and bone disease.

Topics: Aged; alpha-2-HS-Glycoprotein; Blood Proteins; Bone and Bones; Bone Diseases; Calcinosis; Calcium; Calcium-Binding Proteins; Diphosphates; Extracellular Matrix Proteins; Female; Humans; Male; Matrix Gla Protein; Middle Aged; Osteoporosis; Phosphates; Practice Guidelines as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Vascular Diseases

During the past ten years the range of treatments available for patients with osteoporosis has increased greatly. A decade ago the only proven therapy was oestrogen, while today the choice includes bisphosphonates, selective oestrogen receptor modulators, calcitonin, calcium and vitamin D supplementation and, in the near future, parathyroid hormone. Clinical trials involving bone mineral density (BMD) scans of the spine and femur have had an important role in the evaluation of these new therapies. Supplementary information about treatments has been provided by BMD scans of the total body and distal radius as well as by measurements of biochemical markers of bone turnover in serum and urine. Most important of all, the efficacy of treatments has been verified in large trials powered to show reductions in fracture risk. In routine clinical use, BMD scanning has an important role in identifying individual patients with osteoporosis and helping to make decisions about their treatment. However, in contrast to the use of BMD scans in clinical trials, their value for monitoring response to therapy in individual patients is less certain because in many cases the increases in BMD are too small to reliably distinguish between true changes and measurement error. However, experience with well established therapies such as oestrogen and bisphosphonates suggests that these treatments have a beneficial effect on bone in the large majority of patients and individual monitoring of BMD is probably not necessary.

Topics: Biomarkers; Biomedical Research; Bone and Bones; Bone Density; Bone Remodeling; Densitometry; Diphosphates; Diphosphonates; Fractures, Bone; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Predictive Value of Tests

Topics: Bone Resorption; Calcification, Physiologic; Calcinosis; Calcium; Calcium Phosphates; Chemical Precipitation; Dental Calculus; Dihydroxycholecalciferols; Diphosphates; Diphosphonates; Humans; Osteitis Deformans; Osteoporosis; Phosphates; Phosphoric Monoester Hydrolases; Radionuclide Imaging; Structure-Activity Relationship

Pyrophosphate and diphosphonates produce striking results on calcium metabolism in experimental animals and man. Compounds containing P-O-P- bonds (e.g. inorganic pyrophosphate [PP-ii1 or P-C-P bonds (diphosponates) inhibit both the formation and dissolution of calcium phosphate crystals in vitro. PP-i may have a physiological function in regulating calcification and bone turnover, and obnormalities in its metabolism may occur in some human diseases notably hypophosphatasia and pseudogout. Diphosphonates inhibit ectopic calcification, and slow down resorption and bone turnover in several experimental systems in vivo. They have helped in studies of various aspects of the regulation of calcium metabolism. The diphosphonate, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) has been shown in clinical studies to be effective against ectopic calcification particularly in myositis ossificans progressiva and in disorders of increased bone resorption such as Paget's diseases and some types of osteoporosis. -99mTechnetium complexes of EHDP, PP-i and other polyphosphates have also recently been used successfully as bone scanning agents.

Topics: Animals; Bone and Bones; Bone Resorption; Calcification, Physiologic; Calcinosis; Calcium; Calcium Metabolism Disorders; Cartilage; Chemical Phenomena; Chemistry; Culture Techniques; Depression, Chemical; Diphosphates; Etidronic Acid; Humans; Hydroxyapatites; Kidney Diseases; Methylene Chloride; Organophosphonates; Organophosphorus Compounds; Osteoporosis; Urinary Bladder Calculi; Vitamin D

Topics: Adolescent; Aging; Animals; Ascorbic Acid; Bone Development; Calcitonin; Calcium; Collagen; Diphosphates; Female; Glucocorticoids; Gonadal Steroid Hormones; Growth Hormone; Hormones; Humans; Insulin; Osteogenesis; Osteoporosis; Parathyroid Hormone; Phosphates; Potassium; Pregnancy; Rats; Thyroxine; Triiodothyronine; Vitamin A; Vitamin D

Topics: Androgens; Bone Diseases; Diphosphates; Estrogens; Fluorides; Heparin; Humans; Hyperparathyroidism; Metabolic Diseases; Organophosphonates; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Hormone; Phosphates; Plicamycin

Topics: Anemia; Diphosphates; Female; Humans; Menopause; Organophosphonates; Osteoclasts; Osteoporosis; Time Factors

Topics: Bone and Bones; Bone Development; Bone Diseases; Calcitonin; Calcium Metabolism Disorders; Child, Preschool; Densitometry; Diphosphates; Homeostasis; Humans; Hyperparathyroidism; Hypophosphatasia; Hypophosphatemia, Familial; Infant; Metabolism, Inborn Errors; Microradiography; Osteogenesis Imperfecta; Osteoporosis; Parathyroid Glands; Parathyroid Hormone; Phosphorus Metabolism Disorders; Pseudohypoparathyroidism; Rickets; Vitamin D

Topics: Adrenal Cortex Hormones; Aged; Aging; Bone and Bones; Bone Diseases; Bone Resorption; Calcium; Diphosphates; Female; Humans; Hyperparathyroidism; Hypoparathyroidism; Menopause; Metabolic Diseases; Osteogenesis; Osteomalacia; Osteoporosis; Space Flight

Topics: Absorption; Acidosis, Renal Tubular; Alkalies; Aluminum; Biopsy; Bone Diseases; Calcium; Diphosphates; Humans; Hydroxides; Hyperparathyroidism; Hypocalcemia; Kidney Failure, Chronic; Kidney Glomerulus; Magnesium; Ossification, Heterotopic; Osteitis Fibrosa Cystica; Osteomalacia; Osteoporosis; Osteosclerosis; Parathyroid Glands; Phosphates; Radiography; Renal Dialysis; Vitamin D

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor.. To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture.. Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients.. By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not.. While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income.. ClinicalTrials.gov : NCT01401556.

Topics: Administration, Oral; Aged; Alberta; Bone Density Conservation Agents; Case Management; Diphosphates; Female; Humans; Male; Medication Adherence; Middle Aged; Osteoporosis; Osteoporotic Fractures; Patient Education as Topic; Psychometrics; Quality of Life; Recurrence; Secondary Prevention; Socioeconomic Factors; Upper Extremity

The aim of this study was to evaluate the effect of sintered dicalcium pyrophosphate (SDCP) on fracture healing in an osteoporotic rat model. Female Sprague-Dawley rats (8 weeks old) were randomly allocated into five groups: sham-operated group, and bilateral ovariectomized group treated with SDCP, alendronate, calcitonin, or no treatment. Rats were sacrificed at 6 or 16 weeks after fracture. Fracture sites were examined by microcomputed tomography (microCT), histology, and mechanical testing. The results showed that SDCP mildly suppressed callus remodeling at 6 weeks, but not at 16 weeks. The lamellar bone in the callus area and new cortical shell formation in SDCP-treated group were similar to that of the sham group at 16 weeks after fracture, indicating there was no delayed callus remodeling into lamellar bone. At both 6 and 16 weeks after fracture, ultimate stress and elastic modulus were similar between the SDCP and sham groups, and the mechanical strength in these groups was better than that in other groups. Finally, analysis of the serum bone markers CTX-1 and P1NP suggested that SDCP decreased the bone turnover rate and promoted proper fracture healing. The effect of SDCP is superior to that of alendronate and calcitonin in the healing of osteoporotic fractures.

Topics: Animals; Calcium Pyrophosphate; Diphosphates; Drug Combinations; Female; Femoral Fractures; Fracture Healing; Mechanical Phenomena; Osteoporosis; Rats, Sprague-Dawley; X-Ray Microtomography

Bisphosphonate (BP) therapy has modified the natural history of many bone metabolic diseases. Amino-bisphosphonates nowadays represent the primary therapeutic choice for the treatment of osteoporosis and for prevention of fractures. Osteonecrosis of the mandible and maxilla (ONJ) is a rare disease usually occurring in cancer patients with bone metastases treated with high doses of intravenous BPs. Some cases have been described in patients taking amino-BPs for osteoporosis, but the specific drug utilized, its dosage and use of the oral route have reduced that risk considerably (estimated at 1/100,000 subjects a year). Prevention of ONJ include good oral hygiene habits in all patients and, in a subject who has been treated for more than three years, conservative dental procedures when possible, an appropriate antibiotic therapy and a careful follow-up when invasive oral interventions are necessary, are recommended by dentists and bone metabolism experts alike.

Topics: Bone and Bones; Bone Neoplasms; Diphosphates; Dose-Response Relationship, Drug; Female; Humans; Jaw Diseases; Male; Osteonecrosis; Osteoporosis; Risk Factors

The study of our team was driven by a clinical problem of age-dependent chronic degenerative disease of skeleton that includes osteoporosis (OP) and osteoarthritis (OA)-related phenotypes. The major aims of the study included evaluation of the putative genetic factors determining the rate and pattern of the bone and cartilage loss and identification of the specific genes involved in this process. In addition, we examined genetic effects on circulating molecular factors involved in bone and cartilage metabolism. The skeletal phenotypes were assessed from hand radiographs, in total on about 1200 individuals belonging to ethnically homogeneous nuclear and complex three-generational pedigrees of European origin. The results obtained until now can be divided into three sections: (1) genetic analysis of bone mass/size/geometry characteristics (OP) and traits related to hand OA; (2) pedigree-based investigation of circulating levels of calciotropic hormones, growth factors, cytokines, and biochemical indices of bone and cartilage remodelling; (3) linkage and linkage disequilibrium study of several candidate genes, such as estrogen receptor alpha, collagen type I alpha 1, genes related to extracellular inorganic pyrophosphate transport and OP/OA phenotypes, including biochemical variables. The study provides compelling evidence to suggest strong involvement of the genetic factors in determination of variation of the majority of the examined OP- and OA-related phenotypes.

Topics: Age Factors; Aging; Biological Transport; Bone and Bones; Bone Remodeling; Cartilage; Cohort Studies; Collagen Type I; Collagen Type I, alpha 1 Chain; Diphosphates; Estrogen Receptor alpha; Female; Genetic Linkage; Genetic Predisposition to Disease; Genotype; Humans; Likelihood Functions; Linkage Disequilibrium; Male; Models, Biological; Osteoarthritis; Osteoporosis; Pedigree; Phenotype; Risk Factors; Statistics as Topic; Time Factors

Topics: Age Factors; Calcium; Cost of Illness; Diphosphates; Estrogen Replacement Therapy; Hip Fractures; Humans; Osteoporosis; Practice Guidelines as Topic; Public Health; State Medicine; United Kingdom; Vitamin D

Topics: Adult; Child; Diphosphates; Fractures, Bone; Humans; Osteomyelitis; Osteoporosis; Radionuclide Imaging; Spinal Diseases; Spinal Injuries; Spinal Neoplasms; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Arthritis, Rheumatoid; Cartilage, Articular; Collagen; Diphosphates; Humans; Hydroxyapatites; Joints; Necrosis; Osteoporosis

In a group of hospital patients with various diseases, the urinary hydroxyproline-to-creatinine ratio showed a significant correlation (r = 0.63; p less than 0.001) with the 5-hr bone-to-soft-tissue ratio for 99mTc-pyrophosphate uptake. In patients on chronic hemodialysis, a similar correlation was found between the 5-hr bone-to-soft-tissue ratio and hydroxyproline levels in plasma and serum. The findings suggest that 99mTc-pyrophosphate binding by bone is related to collagen metabolism.

Topics: Aged; Bone and Bones; Bone Diseases; Diphosphates; Female; Humans; Hydroxyproline; Hyperparathyroidism; Male; Middle Aged; Osteoporosis; Radionuclide Imaging; Renal Dialysis; Technetium

The authors report the results they obtained by bone scintigraphy using technetium pyrophosphate. In a study of 142 patients with cancer, the authors show, as others have done, that bone scintigraphy makes it possible to find bone metastases that are radiologically undetectable and they emphasize the importance of this discovery. In 7 patients with spondylodiscitis, of whom 1 was without radiological signs at the time the scintigraphy was carried out, the authors always observed localized vertebral hyperfixation and they noted that this examination can be valuable for distinguishing spondylodiscitis from pseudo-Pott's discarthroses and from the lesions of vertebral epiphysitis, which in their experience do not result in isotopic hyperfixation. In 7 patients with epiphyseal osteonecrosis, the authors observed isotopic hyperfixation before the appearance of radiological signs. In 12 patients with osteoporosis, the authors observed hyperfixation in bone in certain compressed vertebrae, whereas other vertebrae that had probably been compressed some considerable time earlier did not fix the isotope excessively. They never observed hyperfixation in vertebrae that were not compressed. Among 5 patients with ankylosing spondylitis with radiological signs of sacro-iliac arthritis, the authors observed sacro-iliac hyperfixation in only 3 cases. Two other patients who had signs indicating ankylosing spondylarthritis, but were without radiological signs of sacro-iliac arthritis did not show sacro-iliac hyperfixation of the isotope. Among 7 patients with Paget's disease, the authors observed hyperfixation in all the bones with radiological signs of disease; in addition, in 3 patients, there was also hyperfixation in certain bones that were radiologically clear.

Topics: Bone Diseases; Bone Neoplasms; Diphosphates; Epiphyses, Slipped; Humans; Joint Diseases; Knee Joint; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteoporosis; Radiography; Radionuclide Imaging; Spinal Diseases; Spondylitis; Spondylitis, Ankylosing; Technetium

The effect of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDPTM) on bone mineral metabolism was tested in 4 healthy young men during 20 weeks of continuous bed rest. Two subjects received an oral dose of 5 mg/kg/day and the other 2 20 mg/kg/day. The low dose had two minor effects: the increase in bone accretion rate which usually occurs during bed rest was prevented, and there was an accentuation of the bed rest induced increase in hydroxyproline excretion. Skeletal mineral loss, assessed by calcium balance measurements and gamma ray absorptiometry of the calcaneus, occurred at the rate previously noted in untreated control subjects. Two types of drug effect were apparent at the higher dosage: one was immediate and sustained--a rise in serum phosphorus concentration and a fall in serum alkaline phosphatase activity. The other was delayed and progressive--a decline in urinary hydroxyproline excretion and in the rates of bone accretion and resorption. Skeletal mineral loss may have been affected; the usual negative mineral balance developed during the first half of the study, then disappeared during the last few weeks. However, gamma ray absorptiometry revealed no attenuation of the calcaneal mineral losses.

Topics: Adult; Alkaline Phosphatase; Bone and Bones; Bone Resorption; Calcium; Depression, Chemical; Diphosphates; Dose-Response Relationship, Drug; Humans; Hydroxyproline; Immobilization; Male; Osteoporosis; Phosphorus; Stimulation, Chemical

Topics: Arthritis; Bone Diseases; Bone Neoplasms; Diagnosis, Differential; Diphosphates; Hodgkin Disease; Humans; Multiple Myeloma; Neoplasm Metastasis; Osteitis Deformans; Osteoarthritis; Osteolysis; Osteomalacia; Osteoporosis; Radionuclide Imaging; Reflex Sympathetic Dystrophy; Rheumatic Diseases; Technetium; Tin

Topics: Alkaline Phosphatase; Cellulose; Cholelithiasis; Diphosphates; Electrophoresis; Hepatitis; Humans; Hyperparathyroidism; Hyperthyroidism; Intestinal Mucosa; Isoenzymes; Jejunum; Kidney Failure, Chronic; Kinetics; Liver; Liver Cirrhosis; Neoplasm Metastasis; Organ Specificity; Osteoporosis; Pyrophosphatases; Regression Analysis; Vinyl Compounds

Topics: Aged; Bone and Bones; Calcitonin; Diphosphates; Endocrine System Diseases; Glycosaminoglycans; Gonadal Steroid Hormones; Growth Hormone; Hormones; Humans; Hydroxyproline; Osteoporosis; Parathyroid Hormone; Thyroid Hormones; Vasopressins

Topics: Adult; Aged; Diphosphates; Glycosaminoglycans; Humans; Hydroxyproline; Middle Aged; Osteoporosis

Topics: Adolescent; Adult; Aged; Bone Diseases; Child; Child, Preschool; Diphosphates; Female; Humans; Hydroxyproline; Hyperparathyroidism; Hyperthyroidism; Male; Middle Aged; Osteitis Deformans; Osteomalacia; Osteoporosis; Parathyroid Glands; Phosphorus Isotopes

Topics: Bone and Bones; Calcium; Dental Caries; Diphosphates; Homeostasis; Hydroxyapatites; Hyperparathyroidism; Hyperthyroidism; Hypophosphatasia; Osteitis Deformans; Osteoporosis; Phosphates; Saliva; Solubility