Osteopenic Postmenopausal Women Research Articles

Bone Turnover Markers Relations to Postmenopausal Osteoporosis

Bone Turnover Markers Relations to Postmenopausal OsteoporosisOsteoporosis is a systemic disease characterized by low bone mass and high bone turnover markers in postmenopausal women (PM). The relationship between biochemical bone markers C-telopeptides of type 1 collagen (CTX) and osteocalcin (OC), and bone mineral density (BMD) in the postmenopausal period was examined in 104 PM women divided into three groups according to their BMD: group A - control PM with normal bone density, group B - osteopenic PM and group C - osteoporotic PM. Mean CTX values were highest in group C (0.54±0.24 ng/mL) compared to group B (0.44±0.21 ng/mL) (p<0.0001), and group A (0.33±0.13 ng/mL) (p<0.029). Mean OC levels in group C (26.83±9.91 ng/mL) were significantly higher compared to group A (20.47±7.03 ng/mL) (p<0.011) but not significantly higher compared to group B (24.11±8.38 ng/mL) (p>0.05). Postmenopause duration was longest in group C (13.1±8.31 yrs) compared to group B (9.6±6.24 yrs), and group A (8.15±6.86 yrs). Postmenopausal women developed osteoporosis with longer menopause duration. PM osteoporotic women were characterized by increased levels of bone turnover markers indicating increased rate of bone remodeling, which resulted in excessive bone resorption, and loss of bone mass. Long-term persistence of high bone resorption marker CTX, insufficiently compensated with bone formation marker OC, enabled osteoporosis development.

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

In a previous study, 12 months after a single annual intravenous dose of 5-mg zoledronate, mean levels of bone resorption markers were 50% to 60% less than the placebo. In another trial, a placebo-controlled randomized study of osteopenic HIV-infected men, bone turnover markers stably decreased for up to 24 months after the second of two annual intravenous doses of 4 mg zoledronate. The duration of action of the currently recommended dose of 5 mg is not known. This double-blind, randomized, placebo-controlled trial, evaluated the duration of the antiresorptive action of a single dose of 5 mg intravenous zoledronate in a volunteer sample of 50 postmenopausal women with osteopenia over a period of 2-year at an academic research center. The participants were randomly assigned to receive a single intravenous infusion of either 5 mg zoledronate (n = 25) or placebo (n = 25). Biochemical markers of bone turnover measured included β-C-terminal telopeptide of type I collagen, N-telopeptide of type 1 collagen, procollagen type-I N-terminal propeptide and serum osteocalcin. Bone mineral density (BMD) of the lumbar spine, proximal femur, and total body was also measured. Compared to the placebo, at 12, 18, and 24 months after administration of the drug, the mean level of each of the 4 bone markers was decreased by at least 38% (range: 38%-64%) (P < 0.0001 for each marker). At 24 months, bone mineral density was higher in the zoledronate group by an average of 5.7% (95% confidence interval [CI], 4.0-7.4) at the lumbar spine; 3.9% (95% CI, 2.2-5.7) at the proximal femur; and 1.7% (95% CI, 0.8-2.5 at the total body (P < 0.0001 for each site). For all markers of bone turnover and BMD measured, between groups, differences were similar at 12 and 24 months. Treatment with zoledronate induced a mild secondary hyperparathyroidism throughout the study. These findings show that the antiresorptive actions of a 5-mg dose of zoledronate persist for 24 months and may be associated with anti-fracture efficacy. There was no evidence that the treatment effect changed over time.

An Observational Study on the Adherence to Treatment Guidelines of Osteopenia

Osteopenia/low bone mineral density (BMD) can lead to osteoporosis and is far more prevalent than osteoporosis. The National Osteoporosis Foundation (NOF) has recommendations for prevention and treatment of low BMD; however, the condition remains underrecognized and undertreated. We assessed practice patterns between physician knowledge of low BMD and prescribing of additional pharmacological therapies as defined by the NOF guidelines. This is a retrospective, observational chart review of electronic medical records of 99 postmenopausal women aged > or =60 years with T-scores between -1.0 and -2.5 on baseline BMD done in 2003 at the Cleveland Clinic Women's Health Center. Counseling, advisement of weightbearing exercise, recommendation of calcium and vitamin D supplementation, and adequate pharmacological therapy in the form of bisphosphonates, hormone therapy, or selective estrogen receptor modulators (SERMs) were assessed. The management of bone specialists credentialed both by the International Society of Clinical Densitometry and the North American Menopause Society and non-bone specialists was also compared. Bone specialists were more likely than non-bone specialists to offer counseling in the form of letters, phone encounters, and follow-up office visits and recommend weightbearing exercises. Most physicians recommended calcium and vitamin D supplementation regardless of specialty. There is no significant difference in the prescribing of pharmacological agents vs. conservative measures for osteopenic postmenopausal women by non-bone specialists vs. bone specialists as defined by the NOF guidelines, such that non-bone specialists did not treat these women any less aggressively than did bone specialists. Osteopenia is adequately managed in our institution regardless of physician group. However, non-bone specialists should consider more direct counseling about bone health and consider advisement of weightbearing exercise.

The bone formation marker N-terminal propeptide of type I collagen is also a marker for fibrogenesis in aged bile duct ligated rats

Po. The analysis was applied to distal radius HR-pQCT scans from the Calgary cohort of the Canadian Multicentre Osteoporosis Study (CaMos), a population-based study of over 9000 women and men in 9 urban centres across Canada. Measurements were compared between 52 premenopausal normal, 70 postmenopausal normal, 98 postmenopausal osteopenic, and 10 postmenopausal osteoporotic women. Using analysis of variance, we found that all postmenopausal groups had higher Ct.Po than the premenopausal group (ranging from 3.6 to 9.2% higher, p<0.001) and both osteopenic and osteoporotic postmenopausal groups had lower Ct.Th than the premenopausal women (−14.5% and−26.0%, both p<0.001, respectively). Dcort was also significantly lower for all postmenopausal womenwhen compared to the premenopausal group (−5.7 to −16.9%, p<0.001). Osteopenic and osteoporotic postmenopausal women both had higher Ct.Po (2.0%, p=0.001 and 5.6%, p<0.001), lower Ct.Th (−12.2% and −24.0%, both p<0.001), and lower Dcort (−6.2% and −11.9%, both p<0.001) than the normal postmenopausal women. Postmenopausal osteoporotic women had 3.9% higher Ct.Po than the osteopenic women (p=0.007) while Ct.Th and Dcort showed no significant difference. These results are consistent with Ct.Th and Dcort trends in other studies (J Clin Endocr Metab 2005 90:6508-15) comparing preand postmenopausal women. Future work will investigate the functional importance of changes in these parameters, particularly porosity, on HR-pQCT estimates of bone strength. Conflict of interest: D. Hanley, Eli Lilly and Amgen, Grant Research Support, Speakers Bureau, Consultant.

Effect of microdose transdermal 17β-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women

Declining estrogen levels after menopause result in bone loss and increased fracture risk. This study investigated whether transdermal microdose 17beta-estradiol (E2) has efficacy and safety comparable to those of raloxifene, a selective estrogen-receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis. This study involved a multicenter, randomized, double-blind, active-controlled, noninferiority trial in 500 osteopenic postmenopausal women comparing transdermal microdose E2 (0.014 mg/d) versus oral raloxifene (60 mg/d), administered for 2 years. Percent change from baseline in bone mineral density at the lumbar spine was measured after 2 years of treatment. Secondary endpoints included proportion of women with no loss of bone mineral density in lumbar spine, change in bone mineral density at hip, biochemical markers of bone turnover, and safety parameters. In the per protocol set, lumbar spine bone mineral density increased by 2.4% (95% CI, 1.9-2.9) with microdose E2 versus 3.0% (95% CI, 2.5-3.5) with raloxifene after 2 years; 77.3% of E2 recipients and 80.5% of those taking raloxifene had no bone loss in the lumbar spine. Both treatments were well tolerated. Most women (99% in the E2 group and 100% in the raloxifene group) showed no histological evidence of endometrial stimulation after 2 years. Mean dense area in breast mammograms was 19.8% in the E2 group versus 19.0% in the raloxifene group after 2 years. Transdermal microdose E2 was similarly effective as raloxifene in preventing bone loss at the lumbar spine. Both treatments were well tolerated, with no clinically significant effect on endometrium or breast density.

Genistein effects on quantitative ultrasound parameters and bone mineral density in osteopenic postmenopausal women

This study aimed at evaluating the effects of genistein (54 mg/die) on calcaneus and phalanges ultrasound (QUS) parameters and bone mineral density in osteopenic postmenopausal women. We concluded that genistein prevented bone loss in the osteopenic postmenopausal women and improves QUS parameters at the calcaneus and phalanges. The purpose of the study was to evaluate the effects of genistein (54 mg/die) on quantitative ultrasound (QUS) parameters of the calcaneus and hand phalange and on bone mineral density (BMD) in osteopenic postmenopausal women. One hundred thirty-eight women (age 49-67 years) were assigned to receive genistein or placebo. Bone status was assessed by measuring the anteroposterior lumbar spine and femoral neck BMD by dual energy X-ray absorptiometry and by ultrasound of the calcaneus (Achilles Plus, GE, Lunar) and of the phalanges (Bone Profiler. IGEA) at baseline and after a 1- and 2-year treatment. At the end of the experimental period, genistein had significantly increased BMD in the femur and lumbar spine (p < 0.001). The stiffness index, amplitude-dependent speed of sound, and bone transmission time in the genistein group had increased significantly at the end of study (+5.3, p < 0.001; +3.6%, p < 0.001; +4.6, p < 0.001, respectively). This study confirms that genistein prevented bone loss in the osteopenic postmenopausal women and it improves the QUS parameters.

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

The effect of group exercise on postmenopausal osteoporosis and osteopenia

We investigated the effects of group exercise on bone mineral density (BMD), pain, and quality of life in postmenopausal women with osteoporosis and osteopenia. The study included 16 osteoporotic (mean age 55.2 years) and 17 osteopenic (mean age 55.4 years) postmenopausal women whose diagnoses were made by dual energy X-ray absorptiometry (DEXA) showing T-scores of less than -2.5 and in a range of -1 to -2.5, respectively. Subjects having orthopedic, neurological, respiratory, vascular, metabolic, or mental problems were excluded. Each group received the same group exercise program for one hour three times a week for 21 weeks, supervised by a physiotherapist, and including breathing, warm-up, stretching, strengthening, balance, stabilization, and cooling exercises. All participants were evaluated before and after the exercise program by a visual analog scale for pain severity, by DEXA for BMD, and by QUALEFFO-41 (Quality of Life Questionnaire of the European Foundation for Osteoporosis) for quality of life. The two groups were similar with respect to age, height, and body mass index (p>0.05), but osteopenic women had a higher body weight (p<0.05). After the exercise program, both groups exhibited significant improvements in T-score, pain score, BMD, and all parameters of the QUALEFFO-41 (p<0.05). The mean T-scores before and after exercise were -2.7 + or - 0.2 and -2.4 + or - 0.5 in osteoporotic women, and -1.8 + or - 0.5 and -1.4 + or - 0.5 in osteopenic women, respectively. Following exercise, 43.8% of osteoporotic women had a T-score showing osteopenia, and 23.5% of osteopenic women had a T-score falling within the normal range. The two groups did not differ significantly with respect to the differences between the mean improvements obtained after the exercise program (p>0.05). This pilot study demonstrates the effectiveness of physiotherapist-supervised group exercise programs in decreasing pain and increasing BMD and quality of life of both osteoporotic and osteopenic women.

The Antiresorptive Effects of a Single Dose of Zoledronate Persist for Two Years: A Randomized, Placebo-Controlled Trial in Osteopenic Postmenopausal Women

Annual iv administration of 5 mg zoledronate decreases fracture risk. The optimal dosing interval of 5 mg zoledronate is not known. Our objective was to determine the duration of antiresorptive action of a single 5-mg dose of iv zoledronate. We conducted a double-blind, randomized, placebo-controlled trial over 2 yr at an academic research center, in a volunteer sample of 50 postmenopausal women with osteopenia. Intervention included 5 mg zoledronate. Biochemical markers of bone turnover and bone mineral density of the lumbar spine, proximal femur, and total body. Compared with placebo, zoledronate treatment decreased mean levels of each of four markers of bone turnover by at least 38% (range 38-45%) for the duration of the study (P < 0.0001 for each marker). After 2 yr, bone mineral density was higher in the zoledronate group than the placebo group by an average of 5.7% (95% confidence interval = 4.0-7.4) at the lumbar spine, 3.9% (2.2-5.7) at the proximal femur, and 1.7% (0.8-2.5) at the total body (P < 0.0001 for each skeletal site). Between-groups differences in markers of bone turnover and bone mineral density were similar at 12 and 24 months. Mild secondary hyperparathyroidism was present throughout the study in the zoledronate group. The antiresorptive effects of a single 5-mg dose of zoledronate are sustained for at least 2 yr. The magnitudes of the effects on markers of bone turnover and bone mineral density are comparable at 12 and 24 months. Administration of zoledronate at intervals of up to 2 yr may be associated with antifracture efficacy; clinical trials to investigate this possibility are justified.

Oral signs and salivary parameters as indicators of possible osteoporosis and osteopenia in postmenopausal women - A study of 45 subjects

Aim: To correlate the oral signs, salivary calcium, phosphorus, alkaline phosphatase levels and dental radiographic findings in postmenopausal osteoporotic, osteopenic and non-osteoporotic women. Materials and Methods: Forty-five subjects were selected based on bone mineral density (BMD) analyses and were assigned to 3 groups (n=15): Group 1 - established osteoporotic women; Group II - established osteopenic women; Group III (control) - non-osteoporotic women. Complete oral and radiographic examination, saliva collection and analysis of calcium, phosphorus and alkaline phosphatase were performed. Results: The results were tabulated and analyzed for statistical significance using the Mann-Whitney U-test. There was statistically significant difference (p<0.05) in salivary calcium, phosphorus and alkaline phosphatase levels when osteoporotic and osteopenic women were compared to the controls. Conclusion: Salivary parameters can be used as indicators to aid in the diagnosis of osteoporosis and osteopenia in postmenopausal women.

Subantimicrobial‐Dose Doxycycline Modulates Gingival Crevicular Fluid Biomarkers of Periodontitis in Postmenopausal Osteopenic Women

We recently demonstrated that a 2-year subantimicrobial-dose doxycycline (SDD) regimen (double-masked, placebo-controlled clinical trial) in postmenopausal (PM) women exhibiting mild systemic bone loss (osteopenia) and local bone loss (periodontitis) reduced the progression of periodontal attachment loss (intent-to-treat analysis) and the severity of gingival inflammation and alveolar bone loss (subgroups) without producing antibiotic side effects. We now describe SDD effects on biomarkers of collagen degradation and bone resorption in the gingival crevicular fluid (GCF) of the same vulnerable subjects. GCF was collected from SDD- and placebo-treated PM subjects (n=64 each) at the baseline and 1- and 2-year appointments; the volume was determined; and the samples were analyzed for collagenase activity (using a synthetic peptide as substrate), relative levels of three genetically distinct collagenases (Western blot), a type-1 collagen breakdown product/bone resorption marker (a carboxyterminal telopeptide cross-link fragment of type I collagen [ICTP]; radioimmunoassay), and interleukin-1beta (enzyme-linked immunosorbent assay). Statistical analyses were performed using generalized estimating equations; primary analyses were intent-to-treat. Collagenase activity was significantly reduced by SDD treatment relative to placebo based on intent-to-treat (P=0.01). ICTP showed a similar pattern of change during SDD treatment, and GCF collagenase activity and ICTP were positively correlated at all time periods (P<0.001). Matrix metalloproteinase (MMP)-8 accounted for approximately 80% of total collagenase in GCF, with much less MMP-1 and -13, and SDD reduced the odds of elevated MMP-8 by 60% compared to placebo (P=0.006). These observations support the therapeutic potential of long-term SDD therapy to reduce periodontal collagen breakdown and alveolar bone resorption in PM women; effects on serum biomarkers of systemic bone loss in these subjects are being analyzed.

Relationship between body mass index and cardiovascular risk factors in osteopenic postmenopausal women

Obese individuals hold an increased risk of several chronic and degenerative diseases including cardiovascular disease (CVD) and diabetes. The present study examined the relationship between body m...

In Vivo Determination of Bone Structure in Postmenopausal Women: A Comparison of HR-pQCT and High-Field MR Imaging

Bone structural measures obtained by two noninvasive imaging tools-3T MRI and HR-pQCT-were compared. Significant but moderate correlations and 2- to 4-fold discrepancies in parameter values were detected, suggesting that differences in acquisition and analysis must be considered when interpreting data from these imaging modalities. High-field MRI and high resolution (HR)-pQCT are currently being used in longitudinal bone structure studies. Substantial differences in acquisition and analysis between these modalities may influence the quantitative data produced and could potentially influence clinical decisions based on their results. Our goal was to compare trabecular and cortical bone structural measures obtained in vivo by 3T MRI and HR-pQCT. Postmenopausal osteopenic women (n = 52) were recruited for this study. HR-pQCT imaging of the radius and tibia was performed using the XtremeCT scanner, with a voxel size of 82 x 82 x 82 microm(3). MR imaging was performed on a 3T Signa scanner using SSFP imaging sequences, with a pixel size of 156 x 156 microm(2) and slice thickness of 500 microm. Structure parameters were calculated using standard HR-pQCT and MRI analysis techniques. Relationships between measures derived from HR-pQCT, MRI, and DXA were studied. Significant correlations between HR-pQCT and MRI parameters were found (p < 0.0001) and were strongest for Tb.N (r(2) = 0.52), Ct.Th (r(2) = 0.59), and site-specific Tb.Sp (r(2) = 0.54-0.60). MRI and HR-pQCT provided statistically different values of structure parameters (p < 0.0001), with BV/TV and Tb.Th exhibiting the largest discrepancies (MR/HR-pQCT = 3-4). Although differences in the Tb.N values were statistically significant, the mean differences were on the order of our reproducibility measurements. Systematic differences between MRI and HR-pQCT analysis procedures leading to discrepancies in cortical thickness values were observed, with MRI values consistently higher. Minimal correlations were found between MRI or HR-pQCT parameters and DXA BMD or T-score, except between HR-pQCT measures at the radius and the ultradistal radius T-scores, where moderate correlations were found (r(2) = 0.19-0.58). This study provides unique insight into two emerging noninvasive tools for bone structure evaluation. Our findings highlight the significant influence of analysis technique on results of in vivo assessment and underscore the importance of accounting for these differences when interpreting results from these modalities.

Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women

A randomized trial was conducted in osteopenic postmenopausal women to compare the efficacy of tibolone versus raloxifene on BMD of the lumbar spine and hip. Tibolone increased lumbar spine and total hip BMD to a statistically significantly greater extent than raloxifene after two years of treatment. Both tibolone, a selective tissue estrogenic activity regulator (STEAR), and raloxifene, a selective estrogen receptor modulator (SERM), are known to prevent postmenopausal bone loss. However, no head-to-head studies to compare the efficacy on bone have been performed. A double-blind, randomized trial was conducted in osteopenic postmenopausal women aged 60-79 years to compare the effects of tibolone 1.25 mg/day to raloxifene 60 mg/day on bone mineral density (BMD). Serum osteocalcin and serum type I collagen C-telopeptides were measured as biochemical markers of bone metabolism. Three hundred and eight subjects were allocated to treatment. Both treatments significantly increased lumbar spine BMD, however the increase was significantly larger after tibolone treatment than after raloxifene treatment (at year 1: 2.2% versus 1.2%, p<0.01 and at year 2: 3.8% versus 2.1%, p<0.001). After 2 years of treatment, the increase in total hip BMD in the tibolone group was significantly larger than in the raloxifene group (p<0.05). Both treatments significantly reduced type I collagen C-telopeptides and osteocalcin levels when compared to baseline. Tibolone 1.25 mg/day for 2 years prevents postmenopausal bone loss in older women and results in a larger increase of BMD both at the lumbar spine and hip than raloxifene.

Effect of risedronate on biochemical marker of bone resorption in postmenopausal women with osteoporosis or osteopenia

Objective. The primary objective of the present study was to evaluate the effectiveness and adverse events of risedronate use in postmenopausal woman by measuring its effects on urinary crosslinked C-terminal telopeptides of type I collagen (CTx), a biochemical marker of bone resorption.Methods. One hundred osteoporotic (control and treatment) and 111 osteopenic (control and treatment) postmenopausal women, selected according to World Health Organization criteria, were included in the study. The treatment groups (osteopenic and osteoporotic) were given risedronate 35 mg once a week. The primary endpoint was mean percentage change in CTx from baseline to 6 months. The secondary endpoints included evaluation of the incidence of clinical or laboratory adverse events occurring during the 6-month study period. The least significant change (LSC), calculated from the within-subject variability in the two control groups, was used to define response.Results. Of the 211 women enrolled, 157 (74.4%) completed the study. After 6 months, urinary CTx levels were −54.7% (range −67% to −48%) below baseline in the osteoporotic treatment group and −66.7% (range −74% to −59%) below baseline in the osteopenic treatment group. Analysis of LSC showed that 89% of risedronate treatment groups were categorized as responders after 6 months of treatment.Conclusion. The study shows that osteoporotic and osteopenic women on risedronate treatment have statistically significant suppressed bone turnover and CTx can be useful to confirm this observation. The low withdrawal rate and adverse effects rate show that risedronate was well tolerated by the study population.

Genistein improves BMD in osteopenic postmenopausal women

Genistein improves BMD in osteopenic postmenopausal women

Subantimicrobial dose doxycycline effects on alveolar bone loss in post‐menopausal women

Determine the efficacy of 2-year continuous subantimicrobial dose doxycycline (SDD; 20 mg bid) on alveolar bone in post-menopausal osteopenic, oestrogen-deficient women undergoing periodontal maintenance in a 2-year double-blind, placebo-controlled, randomized clinical trial. One-hundred and twenty-eight subjects randomized to SDD or placebo (n=64 each). Posterior vertical bite wings taken at baseline, 1 and 2 years for alveolar bone density (ABD), using radiographic absorptiometry (RA) and computer-assisted densitometric image analysis (CADIA), and alveolar bone height (ABH). Statistical analyses utilized generalized estimating equations; primary analyses were intent to treat (ITT). Results are presented as SDD versus placebo. Under ITT, there was no statistically significant effect of SDD on ABD loss (RA: p=0.8; CADIA: p=0.2) or ABH loss (p=0.2). Most sites (81-95%) were inactive. For subgroup analyses, mean CADIA was higher with SDD for non-smokers (p=0.05) and baseline probing depths > or =5 mm (p=0.003). SDD was associated with 29% lower odds of more progressive ABH loss in women >5 years post-menopausal (p=0.05) and 36% lower among protocol-adherent subjects (p=0.03). In post-menopausal osteopenic women with periodontitis, SDD did not differ overall from placebo. Based on exploratory subgroup analyses, additional research is needed to determine the usefulness of SDD in non-smokers, subjects >5 years post-menopausal and in deeper pockets. Protocol registered at (ClinicalTrials.gov). Identifier: NCT00066027.

Strontium ranelate normalizes bone mineral density in osteopenic patients

To assess the capacity of strontium ranelate to restore normal bone mineral density (WHO definition: T-score >or=-1) in post-menopausal osteopenic women (T-score between -1 and -2.5) at baseline. Post-hoc analysis from SOTI and TROPOS studies of 1428 patients randomly assigned to receive either 2 g of strontium ranelate a day or placebo for three years. Bone mineral density was measured at baseline and each year for three years. Results were analyzed on an intention-to-treat basis. At lumbar spine, after one, two and three years of treatment with strontium ranelate, 26.4, 42.1 and 58.2% respectively of osteopenic patients normalized their bone mineral density, compared with 6.6, 8.9 and 11.9% in the placebo group (all p<0.001). At total hip, the percentage of patients normalizing their bone mineral density was 5.4, 10.0 and 19.6% in the strontium ranelate group and 1.8, 1.4 and 1.6% in the placebo one (all p<0.001). Strontium ranelate is able to normalize bone mineral density in a significant proportion of osteopenic patients after one, two and three years of treatment. The clinical relevance of these results should be confirmed by direct demonstration of the anti-fracture efficacy of strontium ranelate in osteopenic patients.

Subantimicrobial Dose Doxycycline Effects on Osteopenic Bone Loss: Microbiologic Results

Based on microbiologic concerns, the safety of a 24-month regimen of subantimicrobial dose doxycycline (SDD; 20 mg twice a day) was evaluated in postmenopausal osteopenic women with periodontitis in a double-blind, placebo-controlled, randomized clinical trial. Subgingival samples were collected from two sites (probing depth > or = 5 mm) in each of 128 subjects at baseline, with the same sites resampled at the conclusion of the 2-year period. The samples were enumerated on selective and non-selective media and on doxycycline (4 microg/ml) medium. Up to five different colonial morphologies were subcultured from the doxycycline medium, identified to species, and susceptibilities determined to doxycycline and five other antibiotics. Data were analyzed for microbial differences in total colony forming units (CFU), periodontal and opportunistic pathogens, and changes in species and in susceptibilities of isolates recovered on doxycycline medium. There was no significant evidence that changes in total anaerobic counts over the treatment period (P = 0.96) differed between treatment groups. Likewise, periodontal pathogens, opportunistic pathogens, or normal flora did not differ descriptively between groups. Although there was a significant increase (P <0.001) in the total CFU recovered from the 4 microg/ml doxycycline plates at 24 months for SDD versus placebo, the percentage that was clinically resistant to doxycycline (minimal inhibitory concentration [MIC] > or = 16 microg/ml) decreased over the 24-month period in both groups and did not differ between the treatment groups (SDD: 79% to 76%; placebo: 83% to 70%; P = 0.2). There were no significant differences (P >0.28 for each) in the change in cross-resistance between the groups for doxycycline and the other five antibiotics. No antimicrobial effect on the subgingival flora was detected following treatment with SDD for 24 months, relative to baseline or to placebo. The increase in initial resistance (at 4 microg/ml) did not translate into a significant increase in the percent resistant to doxycycline (MIC > or = 16 microg/ml) for patients in the SDD group.