Change In Hip Bone Mineral Density Research Articles

Marked increases in bone mineral density and biochemical markers of bone turnover in patients with anorexia nervosa gaining weight

Anorexia nervosa (AN) is a life-threatening eating disorder characterized by an inability to maintain a normal body weight and amenorrhoea, often associated with osteoporosis and increased risk of fragility fractures. Bone metabolism, including markers of bone turnover (serum total alkaline phosphatase, bone alkaline phosphatase [bone AP], osteocalcin [OC] and type I collagen C-telopeptide breakdown products [sCTX]) and bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) at the spine and at the hip, were evaluated in 55 consecutive women with AN undergoing a 3-month intensive nutritional rehabilitation program. The control group was constituted of 25 healthy young medical students. In AN patients body weight increased during the 3-month nutritional program from 37.8 ± 5.1 (mean ± SD) to 51.5 ± 4.5 kg. The corresponding BMI rose to values > 17.5 kg/m 2 in all patients. Mean BMD significantly rose by 2.6 ± 3.5% and 1.1 ± 3.6% at the hip and at the spine, respectively. The markers of bone formation, serum bone AP and osteocalcin, significantly rose by two-folds, while sCTX decreased by 16%. The changes in hip BMD were positively related ( p < 0.005) to changes in body weight and in bone AP ( p < 0.02) while the changes in spine BMD were positively related to changes in serum osteocalcin ( p < 0.05). In the 25 patients who attended the 12-month posttreatment control, mean body weight significantly decreased by 3.6 ± 6.0 kg and this was not associated with any significant change in BMD values. In the patients in whom BMI fell again below 17.5 kg/m 2 hip BMD values decreased significantly. On the contrary, in the patients who maintained BMI > 17.5 kg/m 2, BMD values continued to rise up to values over the 15-month observation of 4.8 ± 6.2 and 7.1 ± 12.1 at the spine and hip, respectively. In conclusion, we have demonstrated that substantial gains in weight in women with chronic AN are associated with remarkable increases in BMD at both the hip and the spine. If weight is maintained, the overall improvement approach 1 SD within 1 year. The changes in both weight and BMD are correlated with improvements in bone formation markers and diminutions in a marker of bone resorption.

The Relationship Between Regional Bone Turnover Measured Using 18F-fluoride Positron Emission Tomography and Changes in BMD Is Equivalent to That Seen for Biochemical Markers of Bone Turnover

Bone turnover is an important determinant of fracture risk. 18F-fluoride positron emission tomography ( 18F-PET) allows the direct assessment of bone turnover at the clinically important skeletal sites such as the lumbar spine. The aim of this study was to determine if the relationship between regional bone turnover measured using 18F-PET and changes in bone mineral density (BMD) is equivalent to that seen for global skeletal measurements of biochemical markers of bone turnover. Forty-three women who had previously had an 18F-PET scan at the lumbar spine, assessment of biochemical markers of bone turnover, and a dual-energy X-ray absorptiometry scan of BMD at the lumbar spine and hip (baseline assessments) were split into 1 of 2 groups: (1) 22 women who commenced treatment for osteoporosis within 2 mo of having the baseline assessments (Treatment group); (2) 21 women who had not taken any treatments for osteoporosis since having the baseline assessments (Untreated group). Sixteen of the women in the Treatment group started risedronate therapy as part of a prospective study they were participating in, whereas the decision to treat the remaining 6 women was made by the subject's treating physician. Subjects had between 2 and 5 BMD scans over a median follow-up time of 4.1 yr to estimate the annual percentage change in BMD since baseline. The relationship between the tertiles of 18F-PET skeletal kinetic parameter K i , reflecting regional bone turnover, and annual changes in lumbar spine and hip BMD were compared to that seen for bone formation (bone-specific alkaline phosphatase, BSALP) and bone resorption (urinary deoxypyridinoline) markers. Treated women in the highest tertile of both regional ( 18F-PET) and global (biochemical markers) bone turnover showed the greatest annual percentage increases in lumbar spine BMD. The annual increase in lumbar spine BMD was 1.8%, 2.2%, and 3.2% for women in the lowest, middle, and highest tertile of BSALP, respectively, which was similar to that obtained for the regional measurement of K i of 1.7%, 2.2%, and 2.7% respectively. Untreated women in the highest tertile of regional and global bone turnover had larger decreases in lumbar spine BMD compared to those women in the lowest tertile, with a 1.4- to 4.8-fold difference in the annual decrease in BMD between the two. Less consistent patterns were observed when assessing the relationship between regional and global bone turnover with changes in hip BMD. This study has demonstrated that the relationship between regional bone turnover measured directly at the lumbar spine with changes in BMD is similar to that seen for global skeletal bone turnover using biochemical markers.

Effects of an Oral Contraceptive (Norgestimate/Ethinyl Estradiol) on Bone Mineral Density in Adolescent Females with Anorexia Nervosa: A Double-Blind, Placebo-Controlled Study

Purpose To evaluate the effect of an oral contraceptive (OC) on bone mineral density (BMD) in adolescent females with anorexia nervosa (AN) or eating disorder not otherwise specified (EDNOS). Methods Females 11–17 years of age with AN or EDNOS entered the study. Subjects were randomized equally to treatment with a triphasic OC containing norgestimate (NGM) 180–250 μg and ethinyl estradiol (EE) 35 μg or placebo for 13 28-day cycles. Dual energy x-ray absorptiometry scans (DXA) of the lumbosacral spine (LS) and hip were obtained at baseline and after 6 and 13 cycles. Results Demographic characteristics of the 112 subjects (NGM/EE 53; Placebo 59) who received study drug and had at least one on-treatment DXA were similar between groups for age (mean: 15 years in each group) and body mass index (mean: NGM/EE 17.9 kg/m 2; Placebo 17.6 kg/m 2). At the end of Cycle 6, there was a significant increase in the mean LS BMD in the NGM/EE group compared with placebo (.020 g/cm 2 vs. .008 g/cm 2; p = .021); however, at the end of Cycle 13 the mean increase in LS BMD in the NGM/EE group compared with placebo was no longer significant (.026 g/cm 2 vs. .019 g/cm 2, p = .244). There was no significant difference in change in hip BMD between groups. The incidence of adverse events was similar between groups. Conclusions In a group of adolescent females with AN or EDNOS, treatment with a triphasic OC for 13 cycles did not have a statistically significant effect on LS or hip BMD.

Soy protein and bone mineral density in older men and women: A randomized trial

Objective Test the hypothesis that soy isoflavone supplementation preserves bone mineral density (BMD) in men and women. Methods We conducted a controlled, parallel-arm, double-blinded trial with 145 participants, 50–80 years, with random assignment to soy beverage daily for 12 months. Active treatment (+ISO) received soy protein containing 83 mg isoflavones (45.6 mg genistein, 31.7 mg daidzein), aglycone units; the comparison group (−ISO) received soy protein containing 3 mg isoflavones. We measured BMD using dual-energy X-ray absorptiometry at the total hip and posterior–anterior spine (L1–L4) at baseline in 22 women and 123 men, and at 12 months in 13 women and 98 men. We used linear mixed models to test for an isoflavone effect on percentage BMD change from baseline in spine and hip. Results Among all participants, mean percent change in spine BMD (±S.E.) was 0.16 ± 0.44 in −ISO ( P = 0.10) at 12 months. Treatment effects on spine BMD were significantly greater in women than men ( P = 0.01). At 12 months, in women, mean percent change was 0.58 ± 0.70 in +ISO and −1.84 ± 0.86 in −ISO ( P = 0.05); among men it was 1.32 ± 0.53 in +ISO and 0.31 ± 0.48 in −ISO ( P = 0.16). By comparison, percent change in hip BMD was similar in the treatment groups, and was not different between men and women. Mean percent change in hip BMD from baseline to 12 months was 0.54 ± 0.38 in +ISO and −0.13 ± 0.36 in −ISO ( P = 0.20) among all participants. Conclusions Soy protein containing isoflavones showed a modest benefit in preserving spine, but not hip BMD in older women.

Weight Loss Is Associated With Loss of Hip BMD in Women

The bone density of women is closely associated with body weight. However, a quantifiable expected change of bone density in relation to weight change is not widely known. PURPOSE: The aim of this study was to quantify the relationship between weight changes (WC) and changes in hip bone mineral density (BMD) in a 4-yr prospective cohort study of 170 middle-aged women. A secondary purpose was to determine the extent differences in baseline weight, age, physical activity (PA), calcium intake, and menopausal status affected the relationship between weight change and hip BMD change. METHODS: All subjects were non-smokers and had BMI's less than 30 at baseline. Average age of the sample was 41.5 ± 2.9 years. BMD was measured at the left hip using DEXA (Hologic 4500W). Body weight was measured using a computerized scale accurate to within 10 grams. Dietary calcium intake was assessed using 7-day weighed food records. Food records were entered into a data base by a registered dietitian and ESHA Research software was used to analyze the diets. Subjects were divided into quartiles based on WC and the middle-two quartiles were collapsed forming three groups classified as Weight Loss (WL) [mean weight change: −5.0 ± 3.4 kg], Low Weight Gain (LWG) [mean weight change: 1.1 ± 1.5 kg], and High Weight Gain (HWG) [mean weight change: 6.8 ± 3.7 kg]. Regression analysis using the general linear model (GLM) technique was employed to quantify the relationship between WC and BMD. RESULTS: Mean weight at baseline was 65.8 ± 10.5 kg and mean WC over the four years was 1.04 ± 5.0 kg. At baseline, mean calcium intake was 773.8 ± 322.3 mg per day. Baseline mean hip BMD was 0.938 ± 0.114 g/cm3 and at follow-up, mean hip BMD was 0.932 ±0.118 g/cm3, a mean change of-0.005 ± 0.036 g/cm3. Changes in hip BMD across the 4 yrs differed as a function of the weight change group (F=7.0, P=0.0012). The WL group had a mean change in BMD of −0.02 g/cm3, whereas the LWG and HWG groups had BMD changes of 0.0001 g/cm3 and 0.0014 g/cm3, respectively. On average, women in the WL group lost 2.5% in hip BMD. For each change in body weight of 10 kg, there was a corresponding change of hip BMD of 0.016 g/cm3 (F=8.5, P=0.004). Adjusting for age and menopause status weakened the relationship. Controlling for PA and calcium intake strengthened the associations. After controlling for all of the confounders together, the association between WC and hip BMD change was significant (F = 6.84, P = 0.0014). CONCLUSIONS: As women lose weight, they also lose BMD at the hip. In the present study, women who lost an average of 5 kg over 4 yrs lost about 2.5% in hip BMD.

High‐impact Step‐aerobic and Progressive Strength Training on Bone Mineral Density in Sedentary Young Women

The purpose of this study was to compare high-impact loaded aerobic exercise and high-intensity strength training on areal bone mineral density (BMD) of the loaded bones in sedentary women, age 20–35 years. Subjects were randomly assigned to: high impact-loaded step aerobic exercise (SA, n=25), high-intensity lower body strength training (ST, n=21) or non-exercise control (CON, n=21). Group differences in BMD were analyzed using ANCOVA. At the 6-month assessment, changes in BMD of the heel (3.5%) and leg (0.9%) were greater (both p<0.05) in the SA than the ST, and change in BMD of total hip and Ward's triangle were greater (p<0.05) in ST (0.3%) than SA (−1.1%). At the 12-month assessment, changes in BMD of the heel in the SA group continued to increase (4.4%, p<0.05). In sedentary young women high-impact activities applied to the heel and lower leg bones produce a positive change in BMD of these two bones, not in bones that are distant from the site of impact. High-intensity strength training of the lower limbs produces a positive change in BMD of the hip and Ward's triangle and not in sites that were distant from the applied force, lumbar spine.

Bone health in urban midlife Malaysian women: risk factors and prevention

The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07+/-5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18-20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm2) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm2) vs. 1.5% (0.020 g/cm2). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm2) and 9.0% (0.122 g/cm2), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm2) and 6.0% (0.138 g/cm2) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm2) at the spine and 1.9% (0.042 g/cm2) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.

A New Active Vitamin D, ED-71, Increases Bone Mass in Osteoporotic Patients under Vitamin D Supplementation: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

ED-71 has been shown to increase lumbar bone mineral density (BMD) in osteoporotic subjects. However, vitamin D insufficiency might have influenced the effect of ED-71 on BMD. Our objective was to examine whether ED-71 can increase BMD in osteoporotic patients under vitamin D supplementation. We conducted a randomized, double-blind, placebo-controlled clinical trial of 219 osteoporotic patients (49-87 yr of age). Subjects were randomly assigned to receive placebo or 0.5, 0.75, or 1.0 microg/d ED-71 for 12 months. All the subjects received 200 or 400 IU/d vitamin D(3). We assessed changes in lumbar and hip BMD and bone turnover markers from baseline. Lumbar BMD increased with ED-71 treatment for 12 months (2.2, 2.6, and 3.1% from baseline and 2.9, 3.4, and 3.8% vs. placebo group in subjects receiving 0.5, 0.75, and 1.0 microg ED-71, respectively). Total hip BMD also increased with 0.75 and 1.0 microg ED-71 (-0.8, 0.6, and 0.9% from baseline and 0.1, 1.5, and 1.8% vs. placebo group in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively). Bone formation and resorption markers were suppressed by approximately 20% after 12 months of 0.75 and 1.0 microg ED-71 treatment. Transient hypercalcemia over 2.6 mmol/liter occurred in 7, 5, and 23% of subjects in the 0.5, 0.75, and 1.0 microg ED-71 groups, respectively, but none of them developed sustained hypercalcemia. These results demonstrate that ED-71 treatment at around 0.75 microg/d can effectively and safely increase lumbar and hip BMD in osteoporotic patients with vitamin D supplementation.

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 μg/ethinyl estradiol 35 μg (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 ≥10 NGM/EE treatment cycles, mean posteroanterior total lumbar spine BMD (L1–L4) increased from 0.881±0.0624 g/cm 2 at baseline (last visit prior to NGM/EE) to 0.894±0.0654 g/cm 2 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.

Longitudinal Study of Changes in Hip Bone Mineral Density in Caucasian and African‐American Women

To determine whether changes in hip bone mineral density (BMD) differ in Caucasian and African American women. Longitudinal study of changes in hip BMD. Four U.S. clinical centers. Six thousand seven Caucasian (mean age 73) and 482 African-American (mean age 75) women enrolled in the Study of Osteoporotic Fractures. Total hip and femoral neck BMD were measured an average of 3.5 years apart (Caucasian) and 2.0 years apart (African American). Annual absolute and percentage changes in BMD and bone mineral apparent density (BMAD) were calculated. The multivariate adjusted annual percentage change in BMD was greater in Caucasian than African-American women at the total hip (-0.574%/y vs -0.334%/y) and femoral neck (-0.515%/y vs -0.203%/y) (both, P<.001). Similar findings were observed for BMAD. The average annualized rate of BMD loss was twice as high in women aged 75 and older as in women younger than 75 in both ethnic groups. The annual percentage loss in femoral neck BMD in nonusers versus hormone therapy users was (-0.57% vs -0.22%) in Caucasians and (-0.35% vs 0.64%) in African Americans (interaction P=.03). The average rate of hip BMD loss is approximately twice as great in Caucasian as African-American women and increases with age in both groups. The hormonal and biochemical factors that contribute to ethnic differences and the increase in bone loss with advancing age need to be identified.

Is there Any Interest in Combining Treatments in Osteoporosis?

Combination therapy includes the concomitant or sequential use of compounds sharing the same mode of action (e.g. two or more inhibitors of bone resorption) or with distinct pathways of activity (e.g. an inhibitor of resorption plus an anabolic agent). Combinatorial use of anti-resorptive agents may generate concerns, due to the risk of inducing oversuppression of bone turnover. However, if low doses of estrogen, used for the management of climacteric symptoms, are insufficient to normalize bone turnover, an addition of a bisphosphonate to HRT can prove to be useful to achieve this objective. Patients pre-treated with inhibitors of resorption, who have no full therapeutic response, are good candidates for the treatment with anabolic agents. The increase in bone turnover that follows the introduction of parathyroid hormone in patients treated with an anti-resorptive agent is similar to that observed in treatment-naive patients and the pattern of bone mineral density (BMD) increase is also identical, with the exception of a 6-month delay in the spine and hip BMD changes observed in prior alendronate-treated subjects. Current data discourage the concomitant use of alendronate and parathyroid hormone since the bisphosphonate appears to blunt, in men and women, the anabolic action of parathyroid hormone. Whether this also applies to other bisphosphonates or inhibitors of resorption remains unknown. The use of an inhibitor of bone resorption after completion of parathyroid hormone treatment seems an appropriate way to maintain the skeletal benefits gained during therapy. Longterm clinical studies, using fractures as an end-point should be initiated to better understand the clinical and pharmaco-economic interest of combination therapies in the management of osteoporosis.

Combination/sequential therapy in osteoporosis

Combination therapy includes the concomitant or sequential use of compounds sharing the same mode of action (eg, two or more inhibitors of bone resorption) or with distinct pathways of activity (eg, an inhibitor of resorption plus an anabolic agent). Combination use of antiresorptive agents may generate concerns, because of the risk of inducing oversuppression of bone turnover. However, if low doses of estrogen, used for the management of climacteric symptoms, are insufficient to normalize bone turnover, the addition of a bisphosphonate to hormone therapy may prove to be useful to achieve this objective. Patients pretreated with inhibitors of resorption, who have not achieved a full therapeutic response, are good candidates for treatment with anabolic agents. The increase in bone turnover that comes after the introduction of parathyroid hormone (PTH) in patients treated with an antiresorptive agent is similar to that observed in treatment-naïve patients and the pattern of bone mineral density (BMD) increase is also identical, with the exception of a 6 month delay in the spine and hip BMD changes observed in prior alendronate-treated subjects. Current data discourage the concomitant use of alendronate and PTH since the bisphosphonate appears to blunt (in men and women) the anabolic action of PTH. Whether this applies to other bisphosphonates or inhibitors of resorption, remains unknown. The use of an inhibitor of bone resorption after completion of PTH treatment seems an appropriate way to maintain the skeletal benefits gained during therapy. Long-term clinical studies, using fractures as an endpoint should be initiated to better understand the clinical and pharmaco-economic interest of combination therapies in the management of osteoporosis.

Healthy elderly individuals do not inevitably lose bone density and weight as they age

There have been relatively few extended longitudinal studies of bone mineral density (BMD) and anthropometric characteristics in the elderly. We recorded baseline measurements (height, weight, body mass index (BMI)) and BMD in 292 relatively healthy individuals (mean age: 75 years females, 76 years males) who were followed up over 8 years. At baseline, a significant inverse relationship was noted between increasing age and BMD at the neck of femur in both sexes. In female subjects, baseline age was inversely related to BMD at the total hip site. There was a significant positive relationship between baseline weight/BMI in both sexes and BMD at the total hip and neck of femur. Weight and BMI were positively related to BMD at the spine in female participants. After a mean follow-up period for males and females of 7.6 and 8.0 years, respectively, there was a significant fall in height for male and female subjects although weight and BMI did not significantly vary in either sex. Follow-up hip BMD fell marginally but significantly in female subjects only. A significant relationship existed between change in hip BMD and change in weight in females. Measurements of the neck of femur did not change significantly on follow-up in either sex. While cross-sectional measurements show weight and age are related to bone density in elderly people, longitudinal evaluation over 8 years failed to demonstrate consistent reductions in males and females. In addition, there was good maintenance of BMD at most sites.

Effect of combined oral estrogen/progestogen preparation (Kliogest®) on bone mineral density, plasma lipids and postmenopausal symptoms in HRT‐naïve Thai women

Kliogest is commonly prescribed for the relief of acute postmenopausal symptoms and prevention of postmenopausal bone loss. However, there have been few data on its effect in Asian women. This 1-year, single-center, randomized, double-blind and placebo-controlled study evaluated the efficacy and safety of Kliogest in hormone replacement therapy (HRT)-naïve Thai women. The subjects were 120 healthy Thai women aged between 45 and 65 years, with intact uterus, and who had been amenorrheic for at least 1 year. Kliogest increased spine (+ 6%, p < 0.01) and hip (+2%, p < 0.01) bone mineral density (BMD), and lowered plasma total cholesterol (TC) (-16%, p < 0.05) and low density lipoprotein cholesterol (LDL-C) (-16%, p < 0.05) concentrations. However, Kliogest also resulted in a decrease in high density lipoprotein cholesterol (HDL-C) concentration (-18%, p < 0.05). Compared to placebo, the reduction in menopausal symptoms by Kliogest was not statistically significant. The frequency and severity of treatment-related uterine bleeding decreased with the duration of Kliogest treatment. Furthermore, there was a fairly strong relationship between the change in serum estrone concentration and the average monthly weighted bleeding scores over the first 6 months (Spearman's correlation r = 0.54; p < 0.001), which became weaker over the entire treatment period (Spearman's correlation r = 0.27; p < 0.01). Although there was a small to moderate relationship between baseline estrone concentration and both lumbar (r = 0.23, p < 0.02) and hip (r = 0.20, p < 0.05) BMD, there was no significant relationship between Kliogest-induced change in estrone concentration and change in lumbar and hip BMD. Continuous treatment with Kliogest for 1 year reversed the potential postmenopausal bone loss in HRT-naïve Thai postmenopausal women. However, its effect on cardiovascular risk is uncertain. Furthermore, Kliogest is safe but appears to have no significant effect on climacteric symptoms in the patients in the present study.

Short-term Administration of Glucagon-like Peptide-2. Effects on Bone Mineral Density and Markers of Bone Turnover in Short-Bowel Patients with No Colon

Background: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of shortbowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. Methods: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 μg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. Results: Mean ± s x (SEM) percent changes in spinal and hip BMD were 1.1 ± 0.4% ( P < 0.05) and 1.9 ± 0.8% ( P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% ( P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. Conclusion: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: A randomized, double-blind, placebo-controlled extension trial

To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Intramuscular clodronate therapy in postmenopausal osteoporosis

Long-term daily administration of oral bisphosphonates has been effective in the treatment of postmenopausal osteoporosis, but the duration, mode and cost of the therapy may sometimes affect patient compliance. In Italy, the bisphosphonate clodronate is also available via the intramuscular (i.m.) route of administration, and the present study was performed to test its efficacy in postmenopausal osteoporosis. Ninety osteoporotic postmenopausal women were enrolled in a randomized, controlled 3 year study. The diet of all patients was adjusted to provide 1200–1300 mg of calcium daily, eventually by administration of supplements. Patients were randomly assigned to no therapy (30 patients) or to receive clodronate 100 mg i.m. either every 2 weeks (30 patients) or 1 week (30 patients). The i.m. injection caused substantial pain at the site of injection, which led to treatment withdrawal in almost 50% of the patients receiving weekly dosing. In control patients, a progressive, slow decline in spine and femoral bone mineral density (BMD), which became statistically significant at the end of the second year of observation, was observed. In the patients given weekly i.m. clodronate, spinal BMD rose by 3.8% (±7.3 SD) within 6 months. A slight, nonsignificant increase was observed thereafter, such that, at the completion of 3 years of observation, the mean gain was 4.5% (±6.3). In the patients treated with injections of 100 mg of clodronate every two weeks the increase in BMD was somewhat lower and slower, becoming significant only at month 24 (2.9 ± 4.6%). In none of the two active groups was the femoral neck BMD changed significantly during the 3 years of the study. A significant increase in trochanter and Ward’s triangle BMD was observed at month 12 only in the patients on the highest dose of clodronate. In both groups treated, the hip BMD changes were significantly different from those observed in control patients. The biochemical markers of bone turnover were suppressed in both clodronate groups. These results indicate that intermittent i.m. clodronate administration can provide clinically relevant benefits to skeletal bone density in osteoporotic postmenopausal women, but the in situ pain may limit its extensive use.

Influence of Clinical Characteristics and Parameters Associated with Thyroid Hormone Therapy on the Bone Mineral Density of Women Treated with Thyroid Hormone

Reports of reduced bone mineral density (BMD) in patients receiving long-term replacement and suppression therapy with L-thyroxine have generated considerable interest and controversy. A substantial literature has evolved, with interpretation of conflicting results obscured by a variety of confounding factors. We examined the BMD measurements of 202 white women who were taking thyroid hormone to determine the contribution to BMD of a number of clinical characteristics and parameters associated with thyroid hormone therapy. Measurements of BMD (N = 335 over 2.6 +/- 1.6 years) of the spine (L2-L4) were performed in 195 subjects. The BMD of three sites of the hip was measured (N = 247 over 1.8 +/- 1.1 years) in 157 subjects. The BMD of the proximal radius was also measured (N = 172 over 1.8 +/- 1.2 years) in 124 subjects. Increasing age and a history of previous thyrotoxicosis had a deleterious effect on spine BMD. Body mass index (BMI) was positively correlated with spine BMD. Dose of thyroid hormone, duration of therapy, type of underlying thyroid disease, history of thyroidectomy, or serum-free thyroxine index did not influence either the initial BMD or the change in spine BMD over time. In the hip, age correlated with a decrease, and BMI with an increase in BMD. A history of previous thyrotoxicosis was associated with a decrease in hip BMD at all three sites (0.05 < p < 0.10). No other clinical parameters significantly influenced either the initial BMD or the change in hip BMD over time. Increasing age and dose of thyroid hormone, and a prior history of thyrotoxicosis had a deleterious effect on the BMD at the proximal radius. In summary, thyroid hormone therapy was not associated with a significant effect on BMD of the spine or hip, but a decreased BMD of the proximal radius was related to both previous thyrotoxicosis and to dose of thyroid hormone.