Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study

Background

This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women.

Study Design

On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra®, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing®, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry.

Results

In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values.

Conclusion

Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.     

Effects of two low-dose combined oral contraceptives containing drospirenone on bone turnover and bone mineral density in young fertile women: a prospective controlled randomized study

BACKGROUND: The effects of a 21-day combined oral contraceptive containing 30 mcg ethinyl estradiol plus 3 mg drospirenone with a 21-day preparation containing 20 mcg ethinyl estradiol plus 3 mg drospirenone on bone turnover and bone mineral density (BMD) in young fertile women were compared. METHODS: A randomized, controlled trial was conducted on healthy fertile women treated with 30 mcg ethinyl estradiol plus 3 mg drospirenone (Group A; n=21), 20 mcg ethinyl estradiol plus 3 mg drospirenone (Group B; n=23) and healthy controls (Group C; n=21). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin (BGP), urinary pyridinoline and deoxypyridinoline were measured. At baseline and after 12 months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry. RESULTS: In Groups A and B, urinary pyridinoline and deoxypyridinoline at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Groups A and B in urinary levels of pyridinoline and deoxypyridinoline, in calcium levels and in BGP levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION: Both combined oral contraceptives exert a similar positive influence on bone turnover in young postadolescent women.     

Increased Intake of Selected Vegetables,Herbs and Fruit may Reduce Bone Turnover in Post-Menopausal Women

Increased consumption of vegetables/herbs/fruit may reduce bone turnover and urinary calcium loss in post-menopausal women because of increased intake of polyphenols and potassium, but comparative human studies are lacking. The main aim was to compare bone turnover markers and urinary calcium excretion in two randomised groups (n = 50) of healthy post-menopausal women consuming ≥9 servings of different vegetables/herbs/fruit combinations (three months). Group A emphasised a generic range of vegetables/herbs/fruit, whereas Group B emphasised specific vegetables/herbs/fruit with bone resorption-inhibiting properties (Scarborough Fair Diet), with both diets controlled for potential renal acid load (PRAL). Group C consumed their usual diet. Plasma bone markers, urinary electrolytes (24 h) and estimated dietary PRAL were assessed at baseline and 12 weeks. Procollagen type I N propeptide (PINP) decreased (−3.2 μg/L, p < 0.01) in the B group only, as did C-terminal telopeptide of type I collagen (CTX) (−0.065 μg/L, p < 0.01) in women with osteopenia compared to those with normal bone mineral density (BMD) within this group. Intervention Groups A and B had decreased PRAL, increased urine pH and significantly decreased urinary calcium loss. Urinary potassium increased in all groups, reflecting a dietary change. In conclusion, Group B demonstrated positive changes in both turnover markers and calcium conservation.     

Effects of an oral contraceptive (norgestimate/ethinyl estradiol) on bone mineral density in women with hypothalamic amenorrhea and osteopenia: an open-label extension of a double-blind, placebo-controlled study

OBJECTIVE: The effects of long-term triphasic oral contraceptive administration on bone mineral density (BMD) were investigated in premenopausal women with hypothalamic amenorrhea (HA) and osteopenia. METHODS: After completing three 28-day cycles in the double-blind phase of a placebo-controlled trial, women (mean age, 26.7 years) who received norgestimate 180-250 microg/ethinyl estradiol 35 microg (NGM/EE, n = 15) or placebo (n = 12) in the double-blind phase were to receive open-label NGM/EE for 10 additional cycles. RESULTS: For subjects completing > or =10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1-L4) increased from 0.881+/-0.0624 g/cm2 at baseline (last visit prior to NGM/EE) to 0.894+/-0.0654 g/cm2 at final visit (p = .043); no significant changes in hip BMD occurred. Decreases in N-telopeptide, osteocalcin, procollagen type I propeptide and bone-specific alkaline phosphatase levels indicated effects on bone metabolism. CONCLUSIONS: Long-term administration of triphasic NGM/EE to osteopenic women with HA may increase total lumbar spine BMD.     

中老年女性骨密度和骨代谢生化指标关系的研究

目的了解中老年女性骨密度和骨代谢生化指标随年龄变化的特点,分析骨代谢生化指标在骨质疏松症早期诊断中的价值。方法测定162例中老年女性腰椎正位骨密度,同时检测所有受检者空腹血清骨钙素、血清碱性磷酸酶及晨尿吡啶啉,尿吡啶啉用肌酐校正。按年龄段和不同骨密度组对骨代谢生化指标值分别进行统计分析。结果骨质疏松在中老年女性中普遍存在,发病率很高,达51.2%。骨代谢指标按年龄分析,中老年女性骨钙素和尿吡啶啉/肌酐在50~69岁时明显升高。70岁以后又趋于下降。而血清碱性磷酸酶各年龄段无显著性差异。按骨密度分析,中老年女性骨质疏松组和骨量减低组的骨钙素和尿吡啶啉/肌酐均明显高于正常组。而骨质疏松组和骨量减低组的骨钙素和尿吡啶啉/肌酐值无显著性差异。各骨密度组的血清碱性磷酸酶无显著性差异。结论骨质疏松症是1种危害极大的疾病,在中老年女性中患病率很高,因此早期诊断尤为重要。血清骨钙素、尿吡啶啉/肌酐分别是反映骨形成和骨吸收特异性和敏感性较高的指标,有助于原发性骨质疏松症的早期诊断。     

Short-term variations in bone remodeling markers of an oral contraception formulation containing 3 mg of drospirenone plus 30 microg of ethinyl estradiol: observational study in young postadolescent women

The clinical study of treated subjects and nontreated controls was made in healthy eumenorrheic young postadolescent women volunteers in the Department of Obstetrics and Gynaecology at Cagliari University, to investigate whether an oral contraceptive (OC) containing drospirenone (3 mg) plus ethinyl estradiol (30 microg) (DRSP+EE) can affect bone metabolism. Control group (n = 26) and OC group (n = 28) women did not differ in age, body mass index, waist-to-hip ratio and main outcome measures [urinary levels of deoxypyridinoline and pyridinoline, serum levels of osteocalcin, bone specific alkaline phosphatase (bSAP), total testosterone (total-T), sex hormone-binding globulin (SHBG), progesterone and bone mineral density (BMD) at the heel]. The control group was studied at the luteal phase (LP) during both the first and the sixth menstrual cycle; the OC group was studied during the first cycle at the LP, and on days 16-18 of the sixth cycle of DRSP+EE treatment. At the sixth cycle, in the control group, the main outcome measures did not change compared to baseline. In the OC group, deoxypyridinoline, pyridinoline, osteocalcin, bSAP, total-T and progesterone levels were reduced, whereas SHBG levels were increased. The BMD was unchanged compared to baseline. The results suggest that 6-month DRSP+EE treatment decreases bone turnover.     

Evidence that treatment with monophasic oral contraceptive formulations containing ethinylestradiol plus gestodene reduces bone resorption in young women

The aim of the study was to evaluate if a pill containing the same dose of the same type of progestin compound (gestodene, GES, 75 microg) but different doses of ethinylestradiol (EE2) (20 or 30 microg) differently influences specific markers of bone resorption (urinary levels of pyridinoline (PYR) and dexoxypyridinoline (D-PYR)). During the 12 months of the study a significant decrease of urinary levels of PYR and D-PYR was found in 2 groups of young post-adolescent women taking the pills with 20 and 30 microg of EE2 in comparison with control women (subjects of the same age group with normal menstrual cycle who did not use contraception). In women taking pills with 20 or 30 microg EE2, the levels of sex hormone-binding globulin (SHBG) significantly increased during treatment in comparison with baseline, whereas in the same time period no changes occurred in control women. These findings suggest that similar to the pill containing 30 microg EE2, the lower dosage of the EE2 pill (20 microg) is also capable of reducing bone resorption. Twenty and 30 microg EE2 pills exert the same biological estrogenic effect. In fact, SHBG levels significantly increased with both pills. However, an additional effect of the progestin compound that could act directly on progestin or estrogen receptors of bone cannot be excluded. Since contraception with a pill containing the lowest estrogen dose is associated with the lowest incidence of side effects, these findings further suggest a pill containing 20 microg EE2 for young post-adolescent women would be the best choice.     

Combined hormonal contraception and bone health: a systematic review

This systematic review examined whether women who use combined hormonal contraception experience changes in risk of fracture or bone mineral density (BMD) that differ from nonusers. We identified 86 articles from PubMed and EMBASE (published 1966 to August 2005) that reported on fracture or BMD outcomes by use of combined hormonal contraceptives. The evidence relating to combined oral contraceptives (COCs) and fracture is inconclusive, as results from the available studies conflict. Studies of adolescent and young adult women generally found lower BMD among COC users than nonusers. Evidence for premenopausal adult women suggested no differences in BMD between COC users and nonusers. COC use in perimenopausal and postmenopausal women preserved bone mass, while nonusers lost BMD, but BMD among former COC users in this age group was the same as for never-users. Evidence for other combined hormonal methods was very limited, with one study indicating no effect of combined hormonal injectable use among premenopausal women on BMD and one study suggesting lower BMD among premenopausal users of the NuvaRing than in nonusers.     

A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 microg or 30 microg ethinylestradiol in combination with levonorgestrel on bone mineral density

In this first prospective, double-blind, randomized, parallel-group study we evaluated the influence of two combined oral contraceptives on bone mineral density (BMD) and metabolic bone parameters. One dose-reduced preparation contained 20 microg ethinylestradiol (EE) in combination with 100 microg levonorgestrel (LNG) (20/100) was compared with the reference preparation which contained 30 microg EE in combination with 150 microg LNG (30/150). Data from 48 volunteers aged 20-35 years were obtained over an observation period of 36 treatment cycles. The direction of the change (increase or decrease) in all investigated bone-related variables was similar in both treatment groups. As compared to baseline, bone mineral density decreased by 0.4% in the 20/100 group and by 0.8% in the 30/150 group after 36 treatment cycles. These changes were not significantly different between the two treatment groups (p = 0.902). For bone-specific alkaline phosphatase, we measured a mean increase of 55.4% (20/100 group) and of 113.2% (30/150 group) after 36 treatment cycles. The two treatments did not differ statistically significantly (p = 0.522). With respect to cross-linked N-telopeptides (NTx), we detected a decrease of the mean NTx urine concentrations of 21.1% (20/100) and of 13.4% (30/150). These changes also did not significantly differ between the two treatments (p = 0.613). Both study treatments were safe and well-tolerated by all volunteers participating in the study. In conclusion, BMD did not change during the 3-year observation period. Thus, both trial preparations containing either 20 or 30 microg EE in combination with LNG were capable of maintaining BMD in young fertile women. There is no reason to assume that the EE dose reduction had any negative impact on BMD. Because there were no differences in BMD between the treatment groups, it can be assumed that even lower dosages than 20 microg EE might be sufficient for bone protection. Biochemical markers provided evidence for a reduced bone resorption.     

Positive effects of a chicken eggshell powder-enriched vitamin-mineral supplement on femoral neck bone mineral density in healthy late post-menopausal Dutch women

Although bone metabolism is largely under genetic control, the role of nutrition is considerable. The present study evaluates the effects of chicken eggshell powder, a new source of dietary Ca, and purified CaCO3 on bone mineral density (BMD) of the lumbar spine and hip. Besides BMD we also looked at biochemical markers of bone and Ca metabolism. Both Ca sources were provided in combination with minerals and vitamins including Mg, cholecalciferol and phylloquinone. We designed a randomised, double-blind, placebo-controlled study to take place over 12 months. Healthy Caucasian women (n 85), selected by age (> or =50 and <70 years), from the databases of general practitioners were recruited by telephone calls. They had to be at least 5 years post-menopausal, with lumbar spine T-score being > - 2.5. At baseline, their mean habitual daily Ca intake was adequate. The women were randomly allocated to: eggshell powder-enriched (group A; n 24), purified CaCO3-enriched (group B; n 22), or a placebo product (group C; n 27). BMD was measured at baseline and then after 6 and 12 months of supplementation as were the biochemical markers bone-specific alkaline phosphatase, amino-terminal propeptide extension of type I collagen, deoxypyridinoline, calcitonin, intact parathyroid hormone, calcidiol, and urinary Ca. After 12 months of supplementation, only mean BMD of the femoral neck in group A was significantly increased (P=0.014) by 1.75% (95% CI 0.18, 3.32) compared with a decrease of -0.60% (95% CI -1.92, 0.72) in group C. This increase coincided with significant decreases in markers of bone resorption and formation. No significant changes were seen in BMD at other sites, including lumbar spine, nor in groups B and C. No differences were found between groups A and B, or B and C. The present study indicates that healthy late post-menopausal women with an adequate Ca intake at baseline may increase BMD of the hip within 12 months following supplementation with the chicken eggshell powder-enriched supplement.     

Efficacy and acceptability of transdermal estradiol in the treatment of postmenopausal bone loss.

In order to assess the effects and acceptability of transdermal estradiol on the prevention of the loss of bone mass, the Authors administered transdermal estradiol (ETTS 50 mcgr/day) for 3 weeks and, cyclically, medroxyprogesterone 10/mg/day from day 10 to day 21 of each cycle for 12 months, to 20 operated patients for bilateral ovariectomy. Primary markers of the bone turnover (hydroxyproline urinary, osteocalcin, PTH) were estimated before therapy and after 3, 6, 9, 12 months. The BMD was evaluated before therapy and after 6 and 12 months. Our study clearly shows that the transdermal administration of estradiol prevents the postmenopausal bone loss, also in postmenopausal women at higher risk of developing osteoporosis as those evaluated in our study.     

Effect of cyclical intravenous clodronate therapy on bone mineral density and markers of bone turnover in patients receiving home parenteral nutrition

BACKGROUND: Patients receiving home parenteral nutrition (HPN) because of intestinal failure are at high risk of developing osteoporosis. OBJECTIVE: We studied the effect of the bisphosphonate clodronate on bone mineral density (BMD) and markers of bone turnover in HPN patients. DESIGN: A 12-mo, double-blind, randomized, placebo-controlled trial was conducted to study the effect of 1500 mg clodronate, given intravenously every 3 mo for 1 y, in 20 HPN patients with a bone mass T score of the hip or lumbar spine of less than -1. The main outcome measure was the difference in the mean percentage change in the BMD of the lumbar spine measured by dual-energy X-ray absorptiometry. Secondary outcome measures included changes in the BMD of the hip, forearm, and total body and biochemical markers of bone turnover, ie, serum osteocalcin, urinary pyridinoline, and urinary deoxypyridinoline. RESULTS: The mean (+/-SEM) BMD of the lumbar spine increased by 0.8 +/- 2.0% in the clodronate group and decreased by 1.6 +/- 2.0% in the placebo group (P = 0.43). At all secondary skeletal sites (ie, hip, total body, and distal forearm), we observed no changes or small increases in the BMD of the clodronate group and decreases in the BMD of the placebo group. In the clodronate group, biochemical markers of bone resorption decreased significantly (P < 0.05). CONCLUSIONS: Clodronate significantly inhibits bone resorption as assessed by changes in biochemical markers of bone turnover. Although the mean BMD increased in the clodronate group, cyclic clodronate therapy failed to increase spinal BMD significantly at 12 mo.     

Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial

This open-label, randomized, Phase III study compared the efficacy and tolerability of and compliance with NuvaRing, a combined contraceptive vaginal ring releasing 15 microg of ethinylestradiol (EE) and 120 microg of etonogestrel daily, with those of and with a combined oral contraceptive (COC) containing 150 microg of levonorgestrel (LNG) and 30 microg of EE. Subjects received NuvaRing or a COC for 13 cycles (3 weeks of ring/pill treatment followed by a 1-week ring-/pill-free period). A total of 1030 subjects (NuvaRing, n=512; COC, n=518) was randomized and started treatment (intent-to-treat [ITT] population). The percentage of women in the ITT population who completed the trial was 70.9% for the NuvaRing group and 71.2% for the COC group. Five in-treatment pregnancies occurred in each group, giving Pearl indices of 1.23 for NuvaRing and 1.19 for the COC. Compliance with both treatments was excellent and both were well tolerated. In conclusion, NuvaRing has comparable efficacy and tolerability with a COC containing 150 microg of LNG and 30 microg of EE and does not require daily dosing.     

Lack of effect of supplementation with essential fatty acids on bone mineral density in healthy pre- and postmenopausal women: two randomized controlled trials of Efacal v. calcium alone

Randomized controlled trials of the effects of the dietary supplement Efacal (Scotia Pharmaceuticals Plc, Guildford, Surrey, UK) v. Ca only on total body bone mineral density (BMD) and markers of bone turnover were conducted in healthy pre- and postmenopausal women separately. Total daily dose for 12 months for the Efacal groups was: Ca 1.0 g, evening primrose oil 4.0 g and marine fish oil 440 mg; and for the control groups was: Ca 1.0 g. Reported compliance was better than 90% in both age groups. For the forty-three premenopausal women (age range 25-40 years), initial mean total body BMD values were similar for Efacal and control groups and both groups showed highly significant mean increases of about 1%; however, there were no significant between-group differences for the changes in BMD or markers of bone turnover. For the forty-two postmenopausal women (age range 50-65 years), initial mean total body BMD values were again well-matched across treatment groups. Both Efacal and control groups showed highly significant decreases in total body BMD of about 1%, but again there were no significant between-group differences in total body BMD or markers of bone turnover. Possible confounding variables such as initial total body BMD were explored but had no effect on the outcome in either age group. Nail quality improved in both age groups and in both Efacal and control groups. Again, there was no significant difference between treatment groups. No evidence was found to support a beneficial effect of Efacal on BMD in these women.     

Comparative effects of dried plum and dried apple on bone in postmenopausal women

Aside from existing drug therapies, certain lifestyle and nutritional factors are known to reduce the risk of osteoporosis. Among the nutritional factors, dried plum or prunes (Prunus domestica L.) is the most effective fruit in both preventing and reversing bone loss. The objective of the present study was to examine the extent to which dried plum reverses bone loss in osteopenic postmenopausal women. We recruited 236 women, 1-10 years postmenopausal, not on hormone replacement therapy or any other prescribed medication known to influence bone metabolism. Qualified participants (n 160) were randomly assigned to one of the two treatment groups: dried plum (100?g/d) or dried apple (comparative control). Participants received 500?mg Ca plus 400?IU (10?μg) vitamin D daily. Bone mineral density (BMD) of lumbar spine, forearm, hip and whole body was assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples were collected at baseline, 3, 6 and 12 months to assess bone biomarkers. Physical activity recall and 1-week FFQ were obtained at baseline, 3, 6 and 12 months to examine physical activity and dietary confounders as potential covariates. Dried plum significantly increased BMD of ulna and spine in comparison with dried apple. In comparison with corresponding baseline values, only dried plum significantly decreased serum levels of bone turnover markers including bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b. The findings of the present study confirmed the ability of dried plum in improving BMD in postmenopausal women in part due to suppressing the rate of bone turnover.     

Modifications of the bone turnover in operated patients of bilateral ovariectomy

The most important factor responsible for osteoporosis postmenopausal is the loss of the oestrogen. For this reason we have estimated the modifications of the bone turnover in the operated patients for bilateral ovariectomy in fertile age by study of the BMD (bone mineral density) and of the various biohumoral parameters that are involved in the process of bone remodelling urinary hydroxyproline, osteocalcin). Our research consists of two phases. I phase: we have conducted a transverse study on a group of 43 patients subdivided in 3 subgroups on the basis of the years elapsed since they were operated. II phase: it is a longitudinal study. We have observed 6 women. We have estimated the turnover before the operation (T0) at (T1), at 30 (T2), at 90 (T3) and at 180 (T4) days from the operation. The results show that the sudden and rapid decrease of the oestrogenic rate determines a sudden increase of the bone turnover. The activity of the osteoblastic line is faster, the activity of osteoblastic line is slower. The beginning of the loss of the bone mass is about the 7% already at six months (longitudinal study), the loss of bone mass reaches the maximum within the first 2-3 years (about 16%) from the operation (transverse study).     

Eating restraint is negatively associated with biomarkers of bone turnover but not measurements of bone mineral density in young women

Relationships among bone mineral density (BMD), bone turnover markers, cortisol, calcium and vitamin D intakes, and cognitive eating restraint score were examined. Sixty-five healthy women, ages 18 to 25 years, had total body, spine, hip, and forearm BMD measured by dual-energy x-ray absorptiometry. Serum osteocalcin, urinary cross-linked N-telopeptide of type I collagen (NTx), and salivary cortisol were measured, and intakes of calcium and vitamin D were estimated from questionnaires. Cognitive eating restraint scores were determined from the Eating Inventory. Associations between measures were analyzed by Pearson correlations; predictors of BMD and bone turnover markers were tested using stepwise regression. Serum osteocalcin (P<0.01) and urinary NTx (P<0.05) were negatively related to cognitive eating restraint score. Intakes of calcium (P<0.05) and vitamin D (P<0.05) were associated with forearm BMD. Regression analyses indicated that vitamin D intake predicted total body (P<0.08) and forearm (P<0.01) BMD. Negative associations between cognitive eating restraint score and bone biomarkers suggest a reduction in bone remodeling, not reflected in current BMD.     

Effects of the long-term use of depot medroxyprogesterone acetate as hormonal contraceptive on bone mineral density and biochemical markers of bone remodeling

PURPOSE AND METHOD: Our objective is to evaluate the effects of the long-term use of depot medroxyprogesterone acetate (DMPA) as a method of contraception on bone mineral density (BMD) and bone remodeling. Forty women (21-44 years old) who used DMPA for contraception for <1, 1-2 and >5 years, in addition to 20 age-matched healthy women (nonusers), participated in this study. Lumbar spine BMD (LS-BMD) was measured by dual-energy X-ray absorptionmetry. Serum osteocalcin (OC), a bone formation marker, was measured by enzyme amplification sorbent immunoassay. Urinary deoxypyridinoline (DPD), a bone resorption marker, was determined by enzyme immunoassay. RESULTS: Serum OC and urinary DPD levels in women who used DMPA for <1, 1-2 and >5 years were significantly increased compared to the corresponding levels in nonusers. The increase of both biomarkers was more pronounced with longer duration of use. LS-BMD was significantly decreased in women on long-term DMPA use compared to LS-BMD in nonusers. The mean percentage decrease of LS-BMD in women who used DMPA for 1-2 and >5 years was 9% and 11.8%, respectively. LS-BMD was negatively correlated with serum OC and urinary DPD in women who used DMPA. On the other hand, LS-BMD and bone turnover were not significantly different between women who used DMPA for <1 year and nonusers. CONCLUSION: Long-term use of DMPA (>2 years) had a significant adverse effect on BMD and induced increased bone turnover, as evidenced by a significant increase in biochemical indices of bone formation and resorption. The measurement of LS-BMD and of biomarkers of bone turnover may be recommended in women aged above 40 years and who used DMPA for a long duration (2-5 years).     

Blood lead levels and bone turnover with weight reduction in women

High bone turnover states are known to raise blood lead levels (BPb). Caloric restriction will increase bone turnover, yet it remains unknown if weight reduction increases BPb due to mobilization of skeletal stores. We measured whole blood Pb levels ((206)Pb) by inductively coupled plasma mass spectrometry in 73 women (age 24-75 years; BMI 23- 61 kg/m(2)) before and after 6 months of severe weight loss (S-WL), moderate weight loss (M-WL), or weight maintenance (WM). Baseline BPb levels were relatively low at 0.2-6.0 microg/dl, and directly associated with age (r=0.49, P<0.0001). After severe WL (-37.4+/-9.3 kg, n=17), BPb increased by 2.1+/-3.9 microg/dl (P<0.05), resulting in BPb levels of 1.3-12.5 microg/dl. M-WL (-5.6+/-2.7 kg, n=39) and WM (0.3+/-1.3 kg, n=17) did not result in an increase in BPb levels (0.5+/-3.2 and 0.0+/-0.7 microg/dl, M-WL and WM, respectively). BPb levels increased more with greater WL (r=0.24, P<0.05). Bone turnover markers increased only with severe WL and were directly correlated with WL. At baseline, higher calcium intake was associated with lower BPb (r=-0.273, P<0.02), however, this association was no longer present after 6 months. Severe weight reduction in obese women increases skeletal bone mobilization and BPb, but values remain well below levels defined as Pb overexposure.     

Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women: no evidence of gene-nutrient interaction with apolipoprotein E polymorphisms

BACKGROUND: Polymorphisms in the apolipoprotein E (APOE) gene are associated with fracture risk, and a potential mechanism is through vitamin K transport. OBJECTIVE: We investigated the relation between dietary vitamin K(1) intake, APOE polymorphisms, and markers of bone health. DESIGN: We measured bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) in a cohort of Scottish women aged 49-54 y in 1990-1994 (baseline) and in 1997-2000 (visit 2). At visit 2, bone markers (urinary pyridinoline crosslinks and serum N-terminal propeptide of type 1 collagen) were measured, 3199 women completed a food-frequency questionnaire, and 2721 women were genotyped for APOE. RESULTS: Compared with quartile 3 (Q3) of energy-adjusted vitamin K(1) intake (mean: 116 microg/d), women in the lowest quartile (mean: 59 microg/d) had lower BMD (analysis of variance; FN, Q1: 0.831 +/- 0.122 g/cm(2); Q3: 0.850 +/- 0.126 g/cm(2); P < 0.001; LS, Q1: 1.000 +/- 0.170 g/cm(2); Q3: 1.020 +/- 0.172 g/cm(2); P = 0.009), remaining significant at the FN after adjustment for age, weight, height, menopausal status or use of hormone replacement therapy, socioeconomic status, and physical activity (P = 0.04). Vitamin K(1) intake was associated with reduced concentrations of pyridinoline crosslinks (Q1: 5.4 +/- 2.0 nmol/mmol; Q4: 5.1 +/- 1.9 nmol/mmol; P = 0.003). Carriers of the E2 allele had greater LS BMD at visit 2 and lost less BMD than did carriers of the E4 allele (E2: -0.50 +/- 1.22%/y; E4: -0.71 +/- 1.17%/y; P = 0.05). After adjustment for confounders, the P value for BMD loss (0.03 for LS and 0.04 for FN) did not reach the level of significance required for multiple testing (P = 0.012). No interaction was observed between dietary vitamin K and APOE on BMD. CONCLUSIONS: Vitamin K(1) intake was associated with markers of bone health, but no interaction was observed with APOE alleles on BMD or markers of bone turnover.