Effects Of Chronic Heroin Abuse On Bone And Mineral Metabolism Pdf

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Osteoporosis is a disease characterized by low bone mass and deterioration of bone structure, which may lead to bone fragility and an increased susceptibility to fractures of the hip or spine, although any bone may be affected. An estimated 10 million Americans are affected by osteoporosis, while an additional 34 million have low bone mass, placing them at an increased risk for osteoporosis. Although there are no overt symptoms in the early stages of osteoporosis, in later stages, patients may experience height loss, change in posture, or pain secondary to a fracture.

Effects of chronic heroin abuse on bone and mineral metabolism

Mean percentage changes from baseline in spine A and total hip B bone mineral density through 36 months of treatment. The differences between each raloxifene hydrochloride group and placebo group and from baseline were statistically significantly different at all time points. Arch Intern Med. Drs Arnaud and Delmas have received honoraria from Eli Lilly Corporation and performed clinical trials of raloxifene supported by Eli Lilly. Dr Cohen is now with R. The studies reported herein evaluated the long-term 3-year effects of raloxifene treatment on bone mineral density BMD , serum lipid levels, and drug tolerability in healthy postmenopausal women.

Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels.

Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years.

These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Raloxifene given to healthy postmenopausal women for 2 years suppressed bone turnover to the normal premenopausal range; increased bone mineral density BMD in the spine, hip, and total body; lowered serum total cholesterol and low-density lipoprotein cholesterol LDL-C levels; and did not stimulate proliferation of the endometrium.

Two clinical trials, each of 5 years' total duration, were identically designed to determine the long-term effects of raloxifene treatment on BMD and lipid levels in healthy postmenopausal women. This analysis includes month data from women enrolled in 2 double-blind, placebo-controlled clinical trials.

Both trials enrolled healthy women, aged 45 through 60 years, and between 2 and 8 years inclusive beyond their last menstrual period at baseline. For both studies, systemic hormone replacement therapy was permitted before, but not during, the study, and only if it had been discontinued at least 6 months before entry. Use of vaginal estrogens, except estradiol, was permitted up to an average of 3 times per week during the study. Concomitant use of progestins, androgens, bone-active agents, or other SERMs was not permitted.

Complete inclusion and exclusion criteria have been published previously. A randomized block design was used to assign women equally to receive daily either raloxifene hydrochloride, 30, 60, or mg, or an identical placebo.

Dietary vitamin D was not supplemented. Study visits were scheduled every 3 months for the first 2 years and every 6 months thereafter. The protocols were approved by local ethical review boards, and all women provided written informed consent for participation in accordance with the principles outlined in the Declaration of Helsinki.

Blood samples were obtained after at least a 6-hour fast every 3 months during the first 2 years, and every 6 months thereafter. Analyses of serum lipid concentrations and routine laboratory measurements were performed centrally using routine methods Covance, Indianapolis and Geneva.

Bone mineral density of the spine L1-L4 , hip, and total body subset of women was measured twice yearly during the first 2 years and annually thereafter by dual energy x-ray absorptiometry using Hologic QDR, , , or machines Hologic, software version 7.

Bone mineral density of the nondominant forearm was determined in a subset of women in study 1 by single energy x-ray absorptiometry Osteometer DTX, software version 1. Scans for a subset of women in study 1 were reanalyzed to determine BMD in the new region of interest N-ROI , a region in the ultradistal forearm with a high content of trabecular bone. At each scheduled visit no less than every 6 months , women were asked in general terms about the occurrence and severity of adverse events.

An adverse event that occurred for the first time or worsened in severity after randomization was considered "treatment-emergent," which does not imply causality. Only treatment-emergent adverse events were analyzed. Women were also asked to grade adverse events as mild, moderate, or severe. If a woman withdrew from the study because of adverse event s , the predominant adverse event contributing to the withdrawal was specifically captured.

All analyses were performed using an intent-to-treat approach. The data set included all women who had at least 1 follow-up visit after randomization. For women who withdrew from the study before the 3-year visit referred to as end point , the last available observation was carried forward to subsequent visits. The changes and percentage changes in BMD from baseline to 6, 12, 18, 24, and 36 months were evaluated by analysis of variance, including a term for therapy and study. Initially, a term for therapy-by-study interaction was included and tested for significance at the.

Since this interaction was not significant, it was deleted from all models. For BMD measurements wherein the therapy effect was significant at the. The changes and percentage changes for biochemical markers of bone turnover and serum lipid levels were not normally distributed Shapiro-Wilk's test of normality.

Median changes were used to represent the central tendency, and SEs for median changes were estimated using the d-delete jackknife method. For measures determined to be normally distributed, means and SDs are presented. For those that were not normally distributed, medians and jackknife SEs are presented. Safety measurements having continuous distribution eg, laboratory results, vital signs were analyzed in a manner similar to efficacy measurements.

Study discontinuations and safety assessments having binary responses eg, adverse events were analyzed using the Cochran-Mantel-Haenszel tests for general association stratified by study. The randomization procedure and identical inclusion and exclusion criteria contributed to similar study groups being enrolled in the 2 trials, as evidenced by the baseline characteristics of enrolled women Table 1.

Treatment responses for key end points were also comparable between studies, and there was no difference between studies in the proportion of women who had withdrawn after 3 years. In the raloxifene groups, there was an increase in spine and total hip BMD during the first 2 years, which was maintained during the third year Figure 1. The response to raloxifene at the femoral neck was similar to the total hip data not shown.

The BMD responses to raloxifene, compared with placebo, were similar across anatomic sites Figure 1 and Table 2. There were no statistically significant differences in the mean percentage changes in spine and hip BMD among raloxifene groups at end point, although the response to mg raloxifene tended to be less than that of the 2 higher doses.

Total body BMD was increased at 3 years by an average of 1. Raloxifene, 60 and mg, significantly attenuated, but did not completely prevent, BMD decline at the ultradistal radius or the forearm new region of interest Table 2. The placebo group also had a slight, but significant, decrease in most markers Table 3.

The responses of serum CrossLaps, serum N-mid osteocalcin, and urine and serum type I collagen fragment N-telopeptide were similar to those of the other bone turnover markers Table 3.

Raloxifene treatment significantly decreased serum total and LDL-C levels Table 4 throughout 3 years, whereas high-density lipoprotein cholesterol HDL-C and triglyceride concentrations were unchanged from baseline after 3 years of raloxifene treatment.

During 3 years of treatment, the tolerability of raloxifene was comparable to that of placebo. The study discontinuation rates were similar across treatment groups, and there were no treatment differences in the reasons for early study withdrawal. Hot flashes were generally mild and did not increase study withdrawals 1. Symptoms usually accompanying hot flashes, such as insomnia and sweating, were not reported more frequently by raloxifene-treated women data not shown.

Other adverse events that have been associated with menopause, therapy with other SERMs, estrogens, or estrogen-progestin replacement therapies were also not reported more frequently during raloxifene therapy compared with placebo Table 5.

Small decreases in markers of bone turnover in the placebo group, possibly attributable to calcium supplementation, were not sufficient to prevent loss of BMD. Data from 2 trials were integrated for this study. The validity of data integration was evidenced by the comparable baseline characteristics and responses to therapy between the 2 studies.

Throughout the follow-up period, the random assignment to therapy and the double-blind were maintained; medication compliance was as expected and was unaffected by drug assignment; and attrition from the study was as expected for an asymptomatic disease prevention study and was unaffected by treatment.

The similarity of BMD responses to raloxifene in different body regions that contain either primarily trabecular ie, spine or cortical bone ie, femoral neck suggests that the effect of raloxifene is similar on these 2 bone types. This is in contrast to other antiresorptive treatment modalities, for example, bisphosphonates, which preferentially increase BMD in the spine.

Thus, the relatively large increase in BMD observed with antiresorptive agents that markedly reduce bone turnover below the normal premenopausal range could be due initially to filling of the remodeling space greatest in cancellous bone and later to an increase in bone mineral per unit volume of bone also greatest in cancellous bone. A similar BMD response to raloxifene in the prevention studies was observed in an osteoporosis treatment trial, Multiple Outcomes of Raloxifene Evaluation MORE , which enrolled osteoporotic women who were about 10 years older at baseline 6 than subjects in the present report.

Although these BMD increases seem modest, patients in MORE treated with raloxifene experienced a significant reduction of risk for incident vertebral fracture at 3 years of therapy. These and other observations suggest that on-treatment change in BMD does not accurately predict clinical outcomes in response to antiresorptive therapies. Whether bone turnover marker responses will prove to be better predictors of fracture prevention efficacy for antiresorptive therapies remains to be determined.

The raloxifene-induced reductions in LDL-C without change in HDL-C or triglyceride concentrations are consistent with previous results, 5 , 18 and indicate that these effects are sustained long-term.

The responses in markers of cardiovascular risk to raloxifene treatment differ from those to oral hormone replacement therapies. In a 6-month study comparing raloxifene with continuous-combined conjugated equine estrogens and medroxyprogesterone acetate HRT , there was a similar effect of the therapies on LDL-C and total cholesterol, whereas raloxifene had a lesser effect on lipoprotein a and no effect on HDL-C. While HRT enhanced fibrinolysis, raloxifene had no effect on fibrinolysis but markedly reduced serum fibrinogen concentration.

The overall tolerability profile of raloxifene in these studies was similar to that of placebo, although a small increase in incident hot flashes was found excess risk, appoximately 7 of treated. Hot flashes were typically reported as mild, were not associated with other symptoms, and did not contribute to study withdrawal.

Importantly, there was no evidence that raloxifene aggravated symptoms or signs of menopause such as vaginitis, and raloxifene therapy was also not associated with symptoms commonly reported during therapy with other SERMs eg, leukorrhea 21 and HRT eg, breast pain, vaginal bleeding. Although reported rarely in these osteoporosis prevention studies, raloxifene therapy has been associated with development of venous thromboembolism in older women, 22 as have HRT 19 and tamoxifen therapy.

In conclusion, raloxifene therapy in healthy, relatively young postmenopausal women resulted in continuous and effective skeletal antiresorptive effects, with decreases in markers of bone turnover and preservation of BMD during 3 years. Raloxifene therapy also reduced serum LDL-C level and was well tolerated.

For these reasons, raloxifene should be considered as an adjunct to exercise and nutritional optimization for long-term osteoporosis prevention in healthy postmenopausal women with risk factors for osteoporosis. Preliminary results showing favorable effects of raloxifene on the risk of breast cancer and the favorable effects on markers of cardiovascular risk suggest that the indications for raloxifene therapy may be broadened in the future. Support was provided by Eli Lilly and Company in the form of research grants to the individual study sites.

The following were principal investigators: Austria: J. Semler, MD Berlin , J. Brandi, MD Florence , C. Papapoulos, MD Leiden , J. Smith, MD, and S. We also gratefully acknowledge the enthusiastic, steady participation of the women volunteers, and the hundreds of skilled and educated research staff. Reprints: C. Our website uses cookies to enhance your experience.

View Large Download. Table 1. Proc Soc Exp Biol Med. Effects of raloxifene on the endometrium in healthy postmenopausal women. Horm Res. Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.

Is Opium Addiction a Risk Factor for Bone Loss?

Combination therapy of curcumin and alendronate modulates bone turnover markers and enhances bone mineral density in postmenopausal women with osteoporosis. This study evaluated the effects of combination therapy of curcumin and alendronate on BMD and bone turnover markers in postmenopausal women with osteoporosis. Each group included 20 patients. Total body, total hip, lumbar spine and femoral neck BMDs were measured by dual-energy X-ray absorptiometry DXA at baseline and after 12 months of therapy. Bone turnover markers such as bone-specific alkaline phosphatase BALP , osteocalcin and C-terminal cross-linking telopeptide of type I collagen CTx were measured at the outset and 6 months later. Patients in the control group suffered a significant decrease in BMD and increased bone turnover markers at the end of study.

Effects of chronic heroin abuse on bone and mineral metabolism. Mario Pedrazzoni, Pier P jects were predominantly involved in manual and agricultural work.

Drug-Induced Osteoporosis

Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Pedrazzoni and P.

Effects of chronic heroin abuse on bone and mineral metabolism.


Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Low bone mineral density BMD prevails among patients with schizophrenia. Antipsychotics use plays an important role in BMD. Previous cross-section study suggests that clozapine treatment may benefit BMD of women with schizophrenia.

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