Decrease In Biochemical Markers Research Articles

Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study.

Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus.

The discovery of a new potent FXR agonist based on natural product screening

FXR agonistic activity screening was conducted based on natural product resources containing 38 structurally diverse sesquiterpenoids isolated from Xylopia vielana. Among them, 34 undescribed sesquiterpenoids with 5 different skeleton types were first characterized by HRESIMS, NMR data, ECD calculations and X-ray crystallographic analysis. High-content screening for FXR agonistic activity of these compounds demonstrated that 13 compounds could activate FXR. Then molecular docking results suggested that hydrogen bonding and hydrophobic interactions might contribute to the main interaction of active compounds with FXR. The preliminary structure–activity relationships (SARs) of those isolates were also discussed. The most potent compound 27 significantly elevated the transcriptional activity of the FXR target gene BSEP promoter (EC50 = 14.26 μM) by a dual-luciferase reporter assay. Western blotting indicated that compound 27 activated the FXR-associated pathway, thereby upregulating SHP and BSEP expression, and downregulating CYP7A1 and NTCP expression. We further revealed that FXR was the target protein of compound 27 through diverse target validation methods, including CETSA, SIP, and DARTS under the intervention of temperature, organic reagents and protease. Pharmacological in vivo experiments showed that compound 27 effectively ameliorated α-naphthyl isothiocyanate (ANIT)-induced cholestasis in mice, as evidenced by the ameliorative histopathology of the liver and the decrease in biochemical markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA). This work showed a practical strategy for the discovery of new FXR agonists from natural products and provided potential insights for sesquiterpenoids as FXR agonist lead compounds.

Prolonged jaundice after previous SARS-CoV-2 infection: a clinical case report

The hepatobiliary system can be affected by a new coronavirus infection (COVID-19), in addition to the respiratory organs. Vanishing bile duct syndrome (VBDS) is a rare cause of jaundice that usually develops as a result of drug-induced liver injury or possibly due to the combined effect of several etiological factors.Clinical case. A 77-year-old patient was hospitalized due to jaundice, skin itching and dark urine. Symptoms first appeared 1 month after COVID-19 treated with ceftriaxone and were accompanied by an increase in biochemical markers of cholestasis. Both extra- and intrahepatic bile ducts injuries were excluded. Liver histology revealed VBDS. Treatment with ursodeoxycholic acid for 11 months led to complete resolution of jaundice, regression of pruritus and a decrease in biochemical markers of cholestasis.Discussion. This clinical case is of interest in connection with the development of VBDS in a patient after coronavirus pneumonia treated with ceftriaxone. VBDS is rarely included in the differential diagnosis of cholestatic syndrome, which is partly due to the lack of awareness of physicians about the complications that develop after COVID-19 and drug therapy.

Effects of Sedi Herba (Sedum sarmentosum) on attenuating cholestasis by the activation of the farnesoid x receptor (FXR)-mediated signaling

Sedum sarmentosum (Sedi Herba) has traditionally been used to treat jaundice and various types of liver disease. This study aimed to clarify the anti-cholestatic efficacy and the mechanism of S. sarmentosum ethyl acetate extract (SDEAE), as well as to screen the potential compounds with FXR activation. SDEAE effectively ameliorated ANIT-induced cholestasis in rats, as evidenced by the ameliorative histopathology of the liver and the significant decrease in biochemical markers (ALT, AST, ALP, GGT, TBIL, DBIL and TBA). The analysis of bile acid profile by LC–MS indicated that SDEAE decreased the toxic bile acid levels (TCA, TMCA and CA). Western blotting indicated that SDEAE activated FXR-associated pathway, thereby upregulating FXR, SHP, BSEP and UGT2B4 expression, and downregulating CYP7A1 and NTCP expression. Twenty-three compounds (7 nor-sesquiterpenoids, 13 flavonoids, 1 lignin, 1 sterol and 1 anthraquinone) were isolated and identified from SDEAE by comparing NMR data with the literature. The HPLC profiles of SDEAE and isolated compounds were also compared. High-content analysis showed that eight compounds (6, 7, 8, 11, 12, 13, 14 and 23) could activate FXR and compound 8 exhibited the most potent activity (p < 0.01). Molecular docking suggested that the main binding modes between these active compounds and FXR were hydrogen bonding and van der Waals forces, and compound 8 had the highest docking score 6.34. The activation of compound 8 on FXR-mediated signaling was validated in L02 cells. After siRNA down-regulation of FXR, compound 8 significantly elevated FXR, SHP, BSEP and UGT2B4 expression, and reduced CYP7A1 and NTCP expression.

Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats.

BackgroundSilver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI).ObjectivesIsoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles.MethodsTwenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO3, and Iso + AgNP groups. AgNPs and silver ion (AgNO3) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue.ResultsThe silver was confirmed in the form of nanoparticles by its size at intervals of 8.72–37.84 nm. Both AgNO3 and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO3 group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity (P < 0.0001 and P < 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO3, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO3 or AgNPs improved the aspartate aminotransferase level.ConclusionThese results suggested that AgNPs have more superior cardioprotective effect compared with AgNO3 against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.

Attenuation of hepatic ischemia‑reperfusion injury by adipose stem cell‑derived exosome treatment via ERK1/2 and GSK‑3β signaling pathways.

Exosomes are an emerging therapeutic tool for the treatment of tissue injuries. In the present study, the protective effect of isolated exosomes from adipose-derived stem cells (ADSCs-exo) against hepatic ischemia-reperfusion (I/R) injury was explored. Hepatic I/R injury was achieved by inducing ischemia for 60 min followed by reperfusion for 2 and 6 h. Pre-treatment with ADSCs-exo revealed a significant reduction in necrosis and apoptosis in liver tissue induced by I/R injury. Hypoxic oxidative stress was managed by exosome-mediated reduced reactive oxygen species and increased superoxide dismutase that in turn protected mitochondrial damage and apoptosis. Reduction in inflammatory mediators such as IL-1β and TNF-α was also observed and protection of hepatocytes from I/R injury was evidenced by a significant decrease in biochemical markers of liver damage (alanine transaminase, aspartate transaminase and lactate dehydrogenase). Exosomal prostaglandin E2 (PGE2)-mediated ERK1/2 and GSK-3β phosphorylation were revealed to increase Bcl-2 and decrease Bax expression with mitochondrial permeability transition pore-inhibition which may be considered a prime mechanism of exosome-mediated hepatoprotection. In conclusion, our results indicated that ADSCs-exo pre-treatment is effective in protecting liver I/R injury.

Inhibition of AngiogenesisIn Vitroby Chebulagic Acid: A COX-LOX Dual Inhibitor

Angiogenesis is a crucial step in the growth of cancer and its metastasis. It is regulated by several endogenous factors which may stimulate or inhibit the new blood vessel growth. Besides these endogenous factors, several exogenous factors including some natural compounds are known to modulate angiogenesis. Angiogenesis being a potential target for drugs against a number of pathological conditions, search for compounds from natural sources that can affect angiogenesis is of great interest. The objective of our present study was to understand the effect of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., on angiogenesis. The model systems used were rat aortic rings and human umbilical vein endothelial cells. The results showed that chebulagic acid exerts an antiangiogenic effect. This was evidenced from decreased sprouting in rat aortic rings and decrease in biochemical markers in endothelial cells treated with chebulagic acid. It downregulated the production of CD31, E-selectin, and vascular endothelial growth factor in human umbilical vein endothelial cells in culture (HUVEC). Further studies to understand the molecular mechanism of action of chebulagic acid revealed that CA exerts its anti angiogenic effect by modulating VE cadherin-β catenin signalling in human umbilical vein endothelial cells.

Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

Background. Loss of bone density with androgen deprivation therapy for prostate cancer is well recognized. We assessed the effects of quarterly infusion of zoledronic acid on bone mineral density (BMD) and markers of bone turnover over a one-year period in men receiving gonadotropin-releasing hormone analog (GnRH-a) for prostate cancer. Methods. 41 subjects were randomly assigned to treatment with zoledronic acid (4 mg) IV infusion or placebo every 3 months. The primary endpoint was the change in the lumbar spine BMD after 12 months of treatment. Results. The change in vertebral BMD in the zoledronic acid group (+7.93 ± 1.4%) was significantly (P < .05) greater than the change in the placebo group (+0.82 ± 1.7%) as was the change in left femoral neck BMD (+5.05 ± 1.4% for the zoledronic acid group versus −0.48 ± 1.4% for the placebo group). The decrease in biochemical markers of bone turnover was significantly (P < .05) greater in the zoledronic acid group compared to the placebo group. Conclusion. Quarterly infusion of zoledronic acid for 1 year improved vertebral and left femoral neck BMD with a decrease in bone turnover markers in men on GnRH-a treatment. Zoledronic acid treatment appears to be promising in men with low BMD receiving GnRH-a treatment.

Colestasis asociada a la nutrición parenteral prolongada en el período neonatal: posible eficacia del ácido ursodesoxicólico

Introduction The morbidity associated with prematurity occasionally leads to the use of prolonged parenteral nutrition, with the subsequent development of cholestasis being one of its complications. Patients and methods This is a two year retrospective study which compared biochemical markers of liver damage and cholestasis in premature babies who received or did not receive urso-deoxycholic acid for parenteral nutrition associated cholestasis. Results Of a total of 24 recruited patients 17 received urso-deoxycholic acid and 7 did not. In the treated group significant decreases ( P<0.05) in gamma-glutamyltranspeptidase and conjugated bilirubin were found after four and five weeks of treatment, respectively. Moreover, a significant correlation ( P<0.01) between conjugated bilirubin and duration of total parenteral nutrition was established. Conclusions Patients who were promptly treated with urso-deoxycholic acid showed a more rapid decrease in biochemical markers of cholestasis, but not of cytotoxicity in the hepatobiliary complications secondary to prolonged parenteral nutrition. However, the present study has limitations derived from its design and therefore it would be desirable launch a randomized trial with sufficient power to evaluate the benefits derived from prophylactic or therapeutic use of urso-deoxycholic acid in the hepatobiliary conditions associated with the prolonged use of parenteral nutrition in the premature infants.

The beneficial effects of inhaled nitric oxide in patients with severe traumatic brain injury complicated by acute respiratory distress syndrome: a hypothesis

BackgroundThe Iraq war has vividly brought the problem of traumatic brain injury to the foreground. The costs of death and morbidity in lost wages, lost taxes, and rehabilitative costs, let alone the emotional costs, are enormous. Military personnel with traumatic brain injury and acute respiratory distress syndrome may represent a substantial problem. Each of these entities, in and of itself, may cause a massive inflammatory response. Both presenting in one patient can precipitate an overwhelming physiological scenario. Inhaled nitric oxide has recently been demonstrated to have anti-inflammatory effects beyond the pulmonary system, in addition to its ability to improve arterial oxygenation. Furthermore, it is virtually without side effects, and can easily be applied to combat casualties or to civilian casualties.Presentation of hypothesisUse of inhaled nitric oxide in patients with severe traumatic brain injury and acute respiratory distress syndrome will show a benefit through improved physiological parameters, a decrease in biochemical markers of inflammation and brain injury, thus leading to better outcomes.Testing of hypothesisA prospective, randomized, non-blinded clinical trial may be performed in which patients meeting the case definition could be entered into the study. The hypothesis may be confirmed by: (1) demonstrating an improvement in physiologic parameters, intracranial pressure, and brain oxygenation with inhaled nitric oxide use in severely head injured patients, and (2) demonstrating a decrease in biochemical serum markers in such patients; specifically, glial fibrillary acidic protein, inflammatory cytokines, and biomarkers of the hypothalamic-pituitary-adrenal axis, and (3) documentation of outcomes.Implications of hypothesisInhaled nitric oxide therapy in traumatic brain injury patients with acute respiratory distress syndrome could result in increased numbers of lives saved, decreased patient morbidity, decreased hospital costs, decreased insurance carrier and government rehabilitation costs, increased tax revenue secondary to occupational rehabilitation, and families could still have their loved ones among them.

Ibandronate produces significant, similar antifracture efficacy in North American and European women: new clinical findings from BONE

ABSTRACTObjectives: BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) determined whether less frequent dosing of ibandronate (dose-free interval > 2 months) provided similar antifracture efficacy to daily dosing. As osteoporosis medications must be effective across different populations, an additional objective of BONE was to investigate and report the effect of oral ibandronate in North American and European women, as described here.Patients and methods: BONE was a randomized, double-blind, placebo-controlled, fracture-prevention study in 2946 postmenopausal women (age 55 years−80 years; ≥ 5 years since menopause) with osteoporosis (low lumbar spine bone mineral density and one to four prevalent vertebral fractures [T4−L4]). Participants received daily calcium (500 mg) and vitamin D (400 IU) plus either placebo, oral daily ibandronate (2.5 mg) or oral intermittent ibandronate (20 mg every other day for 12 doses every 3 months). The efficacy and tolerability of ibandronate were assessed independently in both North American and European populations.Results: Consistent, significant efficacy was observed in the North American (new vertebral fracture risk reduction: 60% and 54% with daily and intermittent ibandronate, respectively) and European patient populations (50% and 48%, respectively). Both ibandronate regimens also significantly reduced the incidence of new, worsening, and acute clinical, vertebral fractures. Daily and intermittent ibandronate significantly increased bone density at the spine in both North American (5.4% and 4.4% vs. baseline with daily and intermittent ibandronate, respectively) and European (7.1% and 6.3% vs. baseline, respectively) populations. Significant increases were also observed for total hip bone density (2.6% and 3.7% vs. baseline for daily, and 2.5% and 3.1% for intermittent; North American and European populations, respectively). Comparable, significant decreases in biochemical markers of bone turnover (reductions in urinary excretion of C-telopeptide levels of 53.5% and 67.1% vs. baseline for daily, and 50.0% and 53.8% for intermittent; North American and European populations, respectively) were also observed in both populations ( p < 0.004 for all cited measurements in each ibandronate group vs. placebo). Oral ibandronate was well tolerated in both North American and European patients, with a safety profile similar to placebo.Conclusions: Oral ibandronate, administered daily or intermittently, effectively reduced vertebral fracture risk in North American and European women with postmenopausal osteoporosis. These results demonstrate the efficacy of ibandronate administered with extended dose-free intervals, regardless of patients’ geographical origin. Research investigating other less frequent ibandronate regimens, such as once-monthly oral administration, is underway.

A Comparison of Oral and Intravenous Bisphosphonate Therapy for Children with Osteogenesis Imperfecta

Bone mineral density and fracture rates in children with osteogenesis imperfecta improve with intravenous bisphosphonates. The efficacy of oral bisphosphonates has not been established. This report is an analysis of an open-label, prospective, randomized clinical trial of oral compared to intravenous bisphosphonate medications in children with osteogenesis imperfecta. Children were stratified according to bone age, pubertal stage, and type of osteogenesis imperfecta and then randomized to receive intravenous pamidronate, 3 mg/kg over 3 days every 4 months, or oral alendronate 1 mg/kg, from a minimum of 10 mg to a maximum of 20 mg daily. The primary efficacy outcome was change in bone mineral density. Secondary outcomes included change in biomarkers of bone turnover, fracture incidence, and growth rate. Ten children were randomized (6 oral and 4 intravenous). Two other children were assigned to intravenous treatment due to chronic abdominal pain. In each group, three patients had type III/IV osteogenesis imperfecta, while three had type I. All 12 children completed 8 months of therapy; nine completed 12 months. Bone mineral density increased in both oral and intravenous groups equally and beyond that expected with normal growth. All children had a decrease in biochemical markers of bone turnover. Linear growth showed a moderate increase above that for age. There was a non-significant decrease in fracture incidence in both groups.

Raloxifene Treatment Is Associated With Increased Serum Estradiol and Decreased Bone Remodeling in Healthy Middle-Aged Men With Low Sex Hormone Levels

In healthy middle-aged men, raloxifene treatment was associated with increased serum estradiol and decreased biochemical markers of bone turnover in subjects with estradiol levels below a threshold of 101.8 pM. We investigated the effects of the selective estrogen receptor modulator raloxifene on bone remodeling in healthy middle-aged men. Forty-three healthy eugonadal men (mean age, 56 years; range, 49-70 years) were enrolled in a randomized placebo-controlled, double-blind, two-sequence crossover study. The subjects received either raloxifene 120 mg/day or placebo for 6 weeks, followed by a 2-month washout period, before crossing over. To predict changes of urinary total deoxypyridinoline/creatinine on raloxifene treatment, we used a logistic regression model to determine cut-off values of sex hormones for highest sensitivity and specificity. In the whole group, raloxifene treatment was associated with an increase in serum sex hormones, that is, total testosterone (+13%, p < 0.01), bioavailable testosterone (+11%, p = 0.02), total estradiol (+11%, p < 0.002), and bioavailable estradiol (+11%, p = 0.035), and with a decrease in serum osteocalcin (-13%, p < 0.05) and serum total alkaline phosphatase (-6%, p < 0.05). Other biochemical markers of bone turnover remained unchanged. Using a logistic regression model to predict changes in urinary deoxypyridoline, we calculated thresholds for total (101.8 pM) and bioavailable (4.79 pM) estradiol, as well as for total (19.4 nM) and bioavailable (0.35 nM) testosterone. Raloxifene treatment was associated with an increase in serum estradiol and decrease in biochemical markers of bone turnover in men with estradiol values below these estradiol thresholds, without any significant change in subjects with values above them. Similarly, raloxifene treatment was associated with an increase in serum testosterone and a decrease in biochemical markers of bone turnover in those with baseline testosterone values below the testosterone thresholds. The association between antiresorptive effects of raloxifene and low sex hormone levels was more pronounced for estradiol than for testosterone. The antiresorptive effect of raloxifene was only detectable in men with low baseline estradiol levels. Unlike in postmenopausal women, the increase of estradiol may contribute to the antiresorptive effect of raloxifene in men.

Efficacy and Safety of Oral Weekly Ibandronate in the Treatment of Postmenopausal Osteoporosis

Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal. Less frequent dosing regimens are likely to improve patient adherence and thus, potentially, patient outcomes. A multicenter, randomized, double-blind, noninferiority study was conducted in 235 women (53-80 yr old; time since menopause >/==" BORDER="0"> 3 yr) with postmenopausal osteoporosis [lumbar spine (L1-L4) bone mineral density (BMD) T-score </= -2] to demonstrate the noninferiority of an oral weekly (20 mg) ibandronate regimen compared with an oral daily (2.5 mg) ibandronate regimen. All patients received daily calcium (500 mg) and vitamin D (400 IU). The primary analysis was the relative change in lumbar spine (L1-L4) BMD from baseline after 48 wk in the per- protocol population. Daily and weekly ibandronate significantly increased spinal BMD by 3.47 and 3.53%, respectively, and provided substantial and similar decreases in biochemical markers of bone turnover. In the primary analysis, noninferiority of the weekly regimen to the daily regimen was demonstrated, with the boundary of the one-sided confidence interval, -0.96%, within both the -1.65% prespecified margin and a more stringent margin of -1.10%. These results demonstrate that oral weekly ibandronate provides the same efficacy and safety as oral daily ibandronate in women with postmenopausal osteoporosis.

Antifibrotic effects of oriental herbs GLM001 on liver cirrhosis induced by bile duct ligation

Liver cirrhosis is characterized by hyperaccumulation of fibrous tissue components and is commonly observed in latter or terminal states of chronic hepatic diseases. In this study, the antifibrotic effects of GLM001 on liver cirrhosis were examined in bile duct ligated rats and patients with hepatic diseases. GLM001 (250 mg/kg rat weight/ day) was administrated to cirrhotic rats for 4 weeks and to humans for 14 weeks. Bile duct ligated rats significantly increased liver collagen content and biochemical markers of hepatic injury. Liver histology showed collagen fiber deposition was increased and the normal architecture was lost with large zones of necrosis being observed frequently. GLM001 administrated rats showed significantly decreased liver collagen content, and accumulation of collagen fiber in histological analysis. Patients, who were treated with GLM001, showed decreases in biochemical markers of hepatic diseases. These results demonstrate the usefulness of GLM001 as an antifibrotic agent for liver cirrhosis.

Fibrous Dysplasia

Definition: Fibrous dysplasia (FD) of bone is a non-inheritable congenital disorder affecting both genders. It is characterized by expanding fibrous lesions, which contain bone-forming mesenchymal cells. Pathophysiology: FD is caused by a somatic activating mutation of the alpha subunit of the Gs protein (Gsα). Bone mesenchymal cells produce a matrix of randomly distributed collagen fibres and islands of woven bone. Osteoclasts are responsible for the spread of the lesions. Clinical Findings: The symptoms are bone pain, fracture, bone deformities and neurological deficits. Spontaneous regression of lesions does not occur. Treatment: Recently, an observational study of treatment with bisphosphonate has yielded promising results. There was a decreased intensity of bone pain, a decrease in biochemical markers of bone turnover and a radiographically apparent ‘refilling of osteolytic sites’ in about half of the patients. Conclusions: Very little is known about the effects of bisphosphonate treatment in children and adolescents with FD. Most patients report decreased bone pain after the first pamidronate infusion, which, in our view, justifies the use of this drug in severely affected patients. The many unanswered questions regarding this form of treatment can only be addressed when a large number of patients is treated in a standardized fashion, and data on the outcome are collected.

Hormone replacement therapy and bone metabolic marker

With the advent of newly developed sensitive markers of bone turnover, initial values of biochemical markers were reported to be significantly higher in those that gained bone than in those that lost bone in hormone replacement therapy (HRT) . Bone resorption markers reach nadir 3 to 6 months after the start of HRT whereas bone formation markers reach nadir 6 month after the treatment. The greater the decrease in biochemical markers is, the larger the bone mass can be expected to be obtained with HRT.

Monitoring individual response to hormone replacement therapy with bone markers

Hormone replacement therapy (HRT) induces a rapid decrease in biochemical markers of bone turnover that correlate with a subsequent increase in bone mineral density (BMD). To determine the utility of bone markers in the management of postmenopausal women receiving HRT, we analyzed the relationship between changes in four markers (serum osteocalcin and bone alkaline phosphatase [BAP], serum and urinary C-telopeptide of type I collagen [CTX]) and changes in spine BMD in 569 women treated for 2 years with different doses of a matrix transdermal 17β-estradiol patch in two placebo-controlled trials. Using a logistic regression model, we found that both the percent change from baseline and the actual value of resorption markers at 3 and 6 months of treatment were predictive of BMD response at 2 years. Comparable results were obtained with formation markers at 6 months only. We determined the sensitivity, probably of positive BMD response, and corresponding cutoff value of markers at 3 and 6 months with a specificity set at a level of 0.90, so that <10% of women classified with markers as responders, i.e., as having a subsequent increase in BMD at 2 years ≥2.26%, would be false positive. All markers provided a high probability of positive BMD response ranging from 0.82 to 0.91, with a sensitivity higher for resorption than for formation markers, and sometimes improved in a model combining the percent change and the actual value of marker under HRT. For example, a decrease in serum CTX ≥ 33% at 3 months of HRT provided a 68% sensitivity and 87% probability of positive BMD response at 2 years for a 90% specificity. At 6 months, a decrease in urinary CTX ≥ 53% provided a 68% sensitivity and 91% probability of a positive BMD response for a 90% specificity. Half of false-negative cases at 3 months will be correctly identified by a subsequent urinary CTX measurement at 6 months. We conclude that the short-term change in bone markers reflects long-term changes of BMD in postmenopausal women treated with HRT. Our data suggest that bone turnover markers can be used to monitor the BMD response to HRT at the individual level. Whether such monitoring could improve long-term compliance to HRT should be tested prospectively.