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ABSTRACT: Context:Serum 25-hydroxyvitamin D (25OHD) is lower in women with darker skin color. Is it due to lower skin production, lower absorption, or different metabolism of vitamin D?Objectives:The objective of the study was to measure the effect of vitamin D3 on serum 25OHD and serum PTH in older African American women with vitamin D insufficiency and the serum 25OHD 20 ng/mL or less (<50 nmol/L). The results can be used to estimate the Recommended Dietary Allowance (RDA).Design and Setting:This was a randomized, double-blind placebo trial at Creighton University Medical Center and Indiana University Medical Center.Participants:Participants were 110 healthy older African American women.Interventions:The intervention consisted of participants randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU daily; calcium supplements were given to maintain total calcium intake of 1200-1400 mg/d.Main Outcome Measurements:Change in serum 25OHD and serum PTH levels at 12 months was measured.Results:Mean baseline serum 25OHD was 13 ng/mL (33 nmol/L). On 4800 IU, serum 25OHD averaged 50 ng/mL (125 nmol/L) compared with 47 ng/mL (117 nmol/L) in Caucasian women. Serum PTH at 12 months decreased significantly (P = .008) when related to serum 25OHD but not dose. Hypercalcemia occurred in 7% and hypercalciuria in 15%. Events were unrelated to vitamin D dose.Conclusion:Vitamin D3 800 IU increased serum 25OHD greater than 20 ng/mL (>50 nmol/L) in 97.5% of the African American women just as it did in the Caucasian women, and therefore, the RDA is the same for both groups. Because absorption and metabolism of oral vitamin D absorption is similar in both groups, lower levels of serum 25OHD in African Americans must be due to lower production of vitamin D in skin.
The Journal of clinical endocrinology and metabolism 02/2013; · 6.50 Impact Factor
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ABSTRACT: Obese people are known to have lower serum 25OHD levels compared to non-obese people. It is not known whether it is due to storage of vitamin D in fat, inadequate input from sunlight, diet or other unknown factors. We examined the relationship at study baseline of serum 25OHD, PTH, 1,25(OH)2D with body composition measurements using Dual energy X-ray Absorptiometry. The results showed a significant inverse relation between total body fat mass and serum 25OHD (p<0.0001) and serum 1,25(OH2)D (p=034) and an independent positive correlation between serum PTH and total body fat mass (p<0.0001). In a randomized controlled study of seven doses of vitamin D (400-4800IU/d) the increase in serum 25OHD levels was compared in women with a normal body mass index to obese women. The response to the low doses of vitamin D (400-800IU/d) was significantly less than that of the medium (1600-2400IU/d) and high doses groups (3200-4800IU) (p<0.0001) in all BMI categories. The increase in serum 25OHD in the medium and high dose groups was not significantly different with increasing level of obesity. But thinner women with a normal BMI (< 25kg/m2) showed a much higher response to vitamin D at any dose level compared to other BMI groups. There was no significant change in total body fat mass after treatment with vitamin D or calcitriol in our randomized trials. In summary, the response to vitamin D is dependent on body weight. Women with BMI <25kg/m2 develop much higher levels of serum 25OHD after vitamin D supplementation compared to those with BMI of >25kg/m2 .The differences in serum 25OHD levels between normal and obese women may be due to differences in volume dilution. After vitamin D supplementation, all obese women reach adequate levels of serum 25OHD but normal women (BMI<25kg/m2) reach much higher levels of 25OHD and in this group smaller doses of vitamin D used should be used.
The Journal of steroid biochemistry and molecular biology 12/2012; · 2.66 Impact Factor
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ABSTRACT: Context: Vitamin D is often recommended for use with calcium supplements to increase absorption. There are no systematic studies of vitamin D on calcium absorption that indicate what dose should be recommended. Objective: Our objective was to study the effect of increasing doses of vitamin D(3) on calcium absorption. Design and Setting: We conducted a randomized double-blind placebo-controlled trial at Creighton University Medical Center, Omaha, NE. Participants: Participants included 163 postmenopausal Caucasian women with vitamin D insufficiency, defined as a serum 25-hydroxyvitamin D (25OHD) below 20 ng/ml (50 nmol/liter). Intervention: Participants were randomized to receive one of the vitamin D(3) doses, 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/d, or placebo for 1 yr. Calcium intake was increased to 1200-1400 mg daily by giving daily calcium citrate. Main Outcome: We evaluated the change in calcium absorption on vitamin D. Results: Mean serum 25OHD increased from baseline 15.6 ng/ml (39 nmol/liter) to 46.5 ng/ml (112 nmol/liter) in subjects randomized to the highest dose of vitamin D (4800 IU). Calcium absorption was more significantly related to serum 25OHD (R(2) = 0.50; P = 0.001) than dose (R(2) = 0.47; P = 0.033). Calcium absorption of a 100-mg dose increased from 52-58% (6 mg) over a serum 25OHD range of 20-66 ng/ml (50-165 nmol/liter). Conclusions: There was no evidence of a threshold for reduced calcium absorption in the serum 25OHD range of 10-66 ng/ml (25-165 nmol/liter). The increase in absorbed calcium of 6% on high doses of vitamin D is so small that the same amount could be obtained from half a glass of milk (100 ml) or 100 mg elemental calcium. The results challenge assumptions about the value of adding vitamin D to increase calcium absorption except when serum 25OHD is very low that is less than 10 ng/ml (25 nmol/liter).
The Journal of clinical endocrinology and metabolism 08/2012; 97(10):3550-6. · 6.50 Impact Factor
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Clifford J Rosen,
Steven A Abrams,
John F Aloia,
Patsy M Brannon,
Steven K Clinton,
Ramon A Durazo-Arvizu, J Christopher Gallagher,
Richard L Gallo,
Glenville Jones,
Christopher S Kovacs,
JoAnn E Manson,
Susan T Mayne,
A Catharine Ross,
Sue A Shapses,
Christine L Taylor
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ABSTRACT: In early 2011, a committee convened by the Institute of Medicine issued a report on the Dietary Reference Intakes for calcium and vitamin D. The Endocrine Society Task Force in July 2011 published a guideline for the evaluation, treatment, and prevention of vitamin D deficiency. Although these reports are intended for different purposes, the disagreements concerning the nature of the available data and the resulting conclusions have caused confusion for clinicians, researchers, and the public. In this commentary, members of the Institute of Medicine committee respond to aspects of The Endocrine Society guideline that are not well supported and in need of reconsideration. These concerns focus on target serum 25-hydroxyvitamin D levels, the definition of vitamin D deficiency, and the question of who constitutes a population at risk vs. the general population.
The Journal of clinical endocrinology and metabolism 03/2012; 97(4):1146-52. · 6.50 Impact Factor
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ABSTRACT: To determine whether titrating up and tapering down of desvenlafaxine (administered as desvenlafaxine succinate) improves its tolerability in postmenopausal women with vasomotor symptoms (VMS).
In the 1-week titration phase, participants received desvenlafaxine 100 mg/d (no titration), desvenlafaxine 50 mg/d, desvenlafaxine 25 mg/d (4 days) then 50 mg/d (3 days), or desvenlafaxine 25 mg/d. Participants then received open-label desvenlafaxine 100 mg/d for 15 weeks. In the 2-week taper phase, participants received placebo, desvenlafaxine 50 mg/d then placebo (7 days each), desvenlafaxine 50 mg/d then 25 mg/d (7 days each), or desvenlafaxine 50 mg/d every other day. Primary endpoints included nausea incidence during the first 2 weeks of treatment and Discontinuation-Emergent Signs and Symptoms (DESS) Checklist total scores after taper weeks 1 and 2.
Nausea incidence was significantly lower for the desvenlafaxine 25 mg/d (19%) and 50 mg/d (22.6%) titration regimens vs. no titration (35.2%; p=0.004 and p=0.035, respectively). At taper week 1, mean DESS scores were significantly lower for desvenlafaxine 50 mg every other day (2.26, p<0.001), 50/25 mg/d (2.28, p<0.001), and 50 mg/d-placebo (1.84, p<0.001) taper regimens vs. no taper (7.07). At week 2, the mean DESS total score was significantly higher for the desvenlafaxine 50 mg/d-placebo regimen vs. no taper (4.46 vs. 2.44, respectively; p=0.009). Desvenlafaxine 50 mg every other day was the least tolerated of the taper regimens.
Titration regimens may improve tolerability of desvenlafaxine 100 mg/d in postmenopausal women with VMS. Taper regimens of desvenlafaxine 50 mg/d-placebo or 50/25-mg/d, were better tolerated than abrupt discontinuation or desvenlafaxine 50 mg given every other day taper regimen.
Journal of Women s Health 02/2012; 21(2):188-98. · 1.57 Impact Factor
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ABSTRACT: The aim of this study was to examine the effect of hormone therapy and calcitriol on depression in older postmenopausal women and to determine whether the response was associated with polymorphisms of estrogen receptor α and vitamin D receptor.
In a double-blind placebo-controlled prospective trial involving 489 postmenopausal older women, a secondary analysis of depression was done. The Geriatric Depression Scale was used to screen for depression. We used binary logistic regression to examine the effect of treatment on depression and one-way analysis of variance to find a relationship between gene polymorphisms and depression.
There was no effect of hormone therapy (odds ratio [OR], 1.65; 95% CI, 0.66-4.12; P = 0.277), calcitriol (OR, 1.15; 95% CI, 0.43-3.11; P = 0.772), or hormone therapy with calcitriol (OR, 1.01; 95% CI, 0.36-2.80; P = 0.979) on depression. Neither the polymorphisms of estrogen receptor α (XbaI-β = 0.093; CI, -0.337 to 1.350; P = 0.239 and PvuII-β = -0.064; CI, -1.171 to 0.491, P = 0.421) nor those of vitamin D receptor (BsmI-β = 0.044, CI -2.546 to 3.030, P = 0.865 and TaqI-β = -0.015, CI -2.900 to 2.738, P = 0.955) were associated with depression.
In older postmenopausal women, there was no effect of hormone therapy and calcitriol either individually or in combination with depression. Estrogen receptor α and vitamin D receptor polymorphisms are not associated with depression or the response to intervention in older postmenopausal women. Additional trials are required to confirm these findings.
Menopause (New York, N.Y.) 12/2011; 19(6):697-703. · 3.08 Impact Factor
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A Catharine Ross,
Joann E Manson,
Steven A Abrams,
John F Aloia,
Patsy M Brannon,
Steven K Clinton,
Ramon A Durazo-Arvizu, J Christopher Gallagher,
Richard L Gallo,
Glenville Jones,
Christopher S Kovacs,
Susan T Mayne,
Clifford J Rosen,
Sue A Shapses
Journal of the American Dietetic Association 10/2011; 111(10):1467. · 3.59 Impact Factor
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ABSTRACT: Millions of women in the United States and across the globe abruptly discontinued postmenopausal hormone therapy (HT) after the initial Women's Health Initiative trial publication. Few data describing the effects of HT cessation on hip fracture incidence in the general population are available. We evaluated the impact of HT cessation on hip fracture incidence in a large cohort from the Southern California Kaiser Permanente health management organization.
In this longitudinal observational study, 80,955 postmenopausal women using HT as of July 2002 were followed up through December 2008. Data on HT use after July 2002, antiosteoporotic medication use, and occurrence of hip fracture were collected from the electronic medical record system. Bone mineral density (BMD) was assessed in 54,209 women once during the study period using the dual-energy x-ray absorptiometry scan.
After 6.5 years of follow-up, age- and race-adjusted Cox proportional hazard models showed that women who discontinued HT were at 55% greater risk of hip fracture compared with those who continued using HT (hazard ratio, 1.55; 95% CI, 1.36-1.77). Hip fracture risk increased as early as 2 years after cessation of HT (hazard ratio, 1.52; 95% CI, 1.26-1.84), and the risk incrementally increased with longer duration of cessation (P for trend < 0.0001). Longer duration of HT cessation was linearly correlated with lower BMD (β estimate [SE]) = -0.13 [0.003] T-score SD unit per year of HT cessation; P < 0.0001).
Women who discontinued postmenopausal HT had significantly increased risk of hip fracture and lower BMD compared with women who continued taking HT. The protective association of HT with hip fracture disappeared within 2 years of cessation of HT. These results have public health implications with regard to morbidity and mortality from hip fracture.
Menopause (New York, N.Y.) 07/2011; 18(11):1172-7. · 3.08 Impact Factor
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ABSTRACT: The aim of this study was to examine the effect of conjugated equine estrogens alone (ET), conjugated equine estrogens + medroxyprogesterone (EPT), calcitriol alone, calcitriol + EPT/ET, or placebo on serum lipid profile and analyze the interaction with estrogen receptor-α gene single nucleotide polymorphisms (ESR-α SNPs) on the response to therapy.
A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlled clinical trial.
In both intent-to-treat and complier (>80% adherent) analysis, there was a significant increase in serum high-density lipoproteins and a significant decrease in serum low-density lipoproteins (LDLs) and the LDL/high-density lipoprotein ratio in all hormone treatment groups compared with placebo (P < 0.05). However, serum triglycerides and very low-density lipoproteins increased in the EPT and ET + calcitriol groups versus placebo (P < 0.05). ESR-α SNPs PvuII and XbaI seemed to have a significant effect on the response to treatment. Genotypes containing the p allele showed a significantly greater decrease in serum cholesterol and very low-density lipoprotein than those having the P allele in the ET + calcitriol group (P < 0.05), and those with the x allele had a significantly greater decrease in serum cholesterol in the hormone therapy + calcitriol group at the end of 3 years versus the X allele, and a greater decrease in serum LDL in alleles x versus the X in the ET + calcitriol group (P < 0.05).
ET with or without progesterone had a favorable effect on lipid profile in postmenopausal older women, and this was dependent on estrogen receptor SNPs--PvuII and XbaI. However, this interaction with ESR-α SNPs needs to be confirmed in larger studies.
Menopause (New York, N.Y.) 06/2011; 18(10):1101-12. · 3.08 Impact Factor
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A Catharine Ross,
Joann E Manson,
Steven A Abrams,
John F Aloia,
Patsy M Brannon,
Steven K Clinton,
Ramon A Durazo-Arvizu, J Christopher Gallagher,
Richard L Gallo,
Glenville Jones,
Christopher S Kovacs,
Susan T Mayne,
Clifford J Rosen,
Sue A Shapses
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ABSTRACT: The Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D comprehensively reviewed the evidence for both skeletal and nonskeletal health outcomes and concluded that a causal role of calcium and vitamin D in skeletal health provided the necessary basis for the 2011 Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for ages older than 1 year. For nonskeletal outcomes, including cancer, cardiovascular disease, diabetes, infections, and autoimmune disorders, randomized clinical trials were sparse, and evidence was inconsistent, inconclusive as to causality, and insufficient for Dietary Reference Intake (DRI) development. The EAR and RDA for calcium range from 500 to 1,100 and 700 to 1,300 mg daily, respectively, for ages 1 year and older. For vitamin D (assuming minimal sun exposure), the EAR is 400 IU/day for ages older than 1 year and the RDA is 600 IU/day for ages 1 to 70 years and 800 IU/day for 71 years and older, corresponding to serum 25-hydroxyvitamin D (25OHD) levels of 16 ng/mL (40 nmol/L) for EARs and 20 ng/mL (50 nmol/L) or more for RDAs. Prevalence of vitamin D inadequacy in North America has been overestimated based on serum 25OHD levels corresponding to the EAR and RDA. Higher serum 25OHD levels were not consistently associated with greater benefit, and for some outcomes U-shaped associations with risks at both low and high levels were observed. The Tolerable Upper Intake Level for calcium ranges from 1,000 to 3,000 mg daily, based on calcium excretion or kidney stone formation, and from 1,000 to 4,000 IU daily for vitamin D, based on hypercalcemia adjusted for uncertainty resulting from emerging risk relationships. Urgently needed are evidence-based guidelines to interpret serum 25OHD levels relative to vitamin D status and intervention.
Journal of the American Dietetic Association 04/2011; 111(4):524-7. · 3.59 Impact Factor
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ABSTRACT: Denosumab treatment for 24 months increased bone mineral density (BMD) and reduced bone turnover markers (BTM) in postmenopausal women.
The aim was to determine the effects of prior denosumab or placebo injections on BMD, BTM, and safety over 24 months after treatment discontinuation.
We conducted an off-treatment extension of a phase 3, randomized, double-blind, parallel-group study.
A total of 256 postmenopausal women with a mean age of 59 yr and a mean lumbar spine T-score of -1.61 at randomization participated in the study.
Participants received placebo or 60 mg denosumab every 6 months for 24 months, followed by 24 months off treatment. Main
We measured the percentage changes in BMD and BTM, and evaluated safety.
Of the 256 participants enrolled in the posttreatment phase, 87% completed the study. During 24 months of denosumab treatment, BMD increased (lumbar spine, 6.4%; total hip, 3.6%; 1/3 radius, 1.4%), and BTM decreased (serum C-terminal telopeptide of type 1 collagen, 63%; and N-terminal propeptide of type 1 procollagen, 47%), compared with placebo. After discontinuation, BMD declined, but the previously treated denosumab group maintained higher BMD than the previously treated placebo group at these sites (P ≤ 0.05). Final BMD at month 48 strongly correlated with month 0 BMD. After denosumab discontinuation, BTM increased above baseline within 3 months (serum C-terminal telopeptide of type 1 collagen) or 6 months (N-terminal propeptide of type 1 procollagen) and returned to baseline by month 48. Adverse event rates during the off-treatment phase were similar between groups.
In postmenopausal women with low BMD, the effects of 60 mg denosumab treatment for 24 months on BMD and BTM are reversible upon discontinuation, reflecting its biological mechanism of action. Residual BMD measurements remained above those of the group previously treated with placebo.
The Journal of clinical endocrinology and metabolism 02/2011; 96(4):972-80. · 6.50 Impact Factor
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ABSTRACT: Osteoporosis is a common postmenopausal disease that has a substantial impact on the quality of life of older women and is associated with significant morbidity and mortality. There are various options for preventing osteoporosis in postmenopausal women, and all are associated with differing benefit-risk profiles. Estrogen therapy (in hysterectomized women) and estrogen/progestogen therapy (in nonhysterectomized women) are the most effective treatments available for the relief of vasomotor and urogenital symptoms in postmenopausal women and provide significant protection against osteoporotic fractures. Selective estrogen receptor modulators reduce bone loss and prevent vertebral fractures without endometrial or breast stimulation. Raloxifene, the only selective estrogen receptor modulator approved for osteoporosis prevention and treatment, significantly reduces vertebral but not nonvertebral or hip fractures. Bisphosphonates prevent bone loss and vertebral fractures; however, not all bisphosphonates have been shown to prevent nonvertebral fractures. Selective estrogen receptor modulators and bisphosphonates are not effective for menopausal symptoms. Hormone therapy should be considered as first-line therapy for preventing bone loss and fractures in early postmenopausal women who are symptomatic; other options include selective estrogen receptor modulators and bisphosphonates, especially in older, nonsymptomatic women. Future therapies are likely to include newer selective estrogen receptor modulators, combinations of estrogen with selective estrogen receptor modulators, and denosumab.
Menopause (New York, N.Y.) 01/2011; 18(1):109-18. · 3.08 Impact Factor
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A Catharine Ross,
JoAnn E Manson,
Steven A Abrams,
John F Aloia,
Patsy M Brannon,
Steven K Clinton,
Ramon A Durazo-Arvizu, J Christopher Gallagher,
Richard L Gallo,
Glenville Jones,
Christopher S Kovacs,
Susan T Mayne,
Clifford J Rosen,
Sue A Shapses
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ABSTRACT: This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age. For vitamin D, RDAs of 600 IU/d for ages 1-70 yr and 800 IU/d for ages 71 yr and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter), meet the requirements of at least 97.5% of the population. RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer. Higher values were not consistently associated with greater benefit, and for some outcomes U-shaped associations were observed, with risks at both low and high levels. The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated. Urgent research and clinical priorities were identified, including reassessment of laboratory ranges for 25-hydroxyvitamin D, to avoid problems of both undertreatment and overtreatment.
The Journal of clinical endocrinology and metabolism 01/2011; 96(1):53-8. · 6.50 Impact Factor
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BMJ (Clinical research ed.). 01/2011; 342:d4046.
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ABSTRACT: To evaluate the efficacy of the tissue-selective estrogen complex, bazedoxifene/conjugated estrogens (BZA/CE), for postmenopausal osteoporosis prevention.
Multicenter, randomized, double-blind, placebo- and active-controlled, phase 3 trial (Selective estrogen Menopause And Response to Therapy [SMART]-1).
Outpatient clinical study.
Women (n = 3,397) more than 5 years and 1-5 years postmenopause were enrolled in the Osteoporosis Prevention I and II Substudies, respectively.
Single tablets of BZA (10, 20, or 40 mg) each with CE (0.625 or 0.45 mg), raloxifene (60 mg), or a placebo taken daily for 2 years.
The primary outcome for both substudies was change in bone mineral density of the lumbar spine; bone mineral density was also measured at the hip.
In both substudies, bone mineral density increased significantly more with all BZA/CE doses compared with placebo at the lumbar spine and total hip, and for most BZA/CE doses compared with raloxifene at the lumbar spine. Osteocalcin and N-telopeptide significantly decreased with all BZA/CE doses vs. placebo and most BZA/CE doses vs. raloxifene.
BZA/CE combinations decreased bone turnover and bone loss in postmenopausal women at increased risk for osteoporosis.
Fertility and sterility 08/2009; 92(3):1045-52. · 3.97 Impact Factor
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J Christopher Gallagher
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ABSTRACT: This Practice Point commentary discusses a double-blind, placebo-controlled trial by Cummings et al. that investigated the effects of tibolone 1.25 mg per day in 4,534 postmenopausal women (mean age 68 years) with osteoporosis. Tibolone is a synthetic steroid with estrogenic, progestational and androgenic effects. It has been used as an alternative to estrogen to treat menopausal symptoms for 30 years. Cummings et al. found that tibolone reduced the incidence of vertebral fractures by 45%, nonvertebral fractures by 26%, breast cancer by 68% and colon cancer by 69%. The trial was discontinued 2 months before a median treatment time of 3 years because the major end point (reduction of fractures) was reached. In addition, tibolone increased the risk of stroke, although the absolute risk was small. Similarly to other compounds with estrogenic activity that increase the risk of stroke, such as estrogen and selective estrogen-receptor modulators, clinicians must weigh the risks and benefits of therapy for individual patients. This risk might be lower in women aged 50-60 years than in those aged >60 years.
Nature Clinical Practice Endocrinology & Metabolism 01/2009; 5(3):128-9. · 7.55 Impact Factor
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ABSTRACT: Decreased calcitriol production due to impaired renal function may be a significant risk factor for falls in normal aging population.
The objective of the study was to examine the association between creatinine clearance (CrCl) and the incidence of falls and fallers in groups treated with placebo, calcitriol, estrogen therapy (ET)/estrogen + progestin therapy (HT), and calcitriol + ET/HT.
This was a 3-yr, double-blind, placebo-controlled study designed to test the efficacy of calcitriol and ET/HT on bone loss and falls with analysis by intention to treat and post hoc.
The study was conducted at an academic outpatient center.
Four hundred eighty-nine normal elderly women aged 65-77 yr; 415 women completed the study.
Subjects were randomized to placebo, calcitriol 0.25 mug twice a day, ET daily (conjugated equine estrogens 0.625 mg), HT (conjugated equine estrogen 0.625 mg + medroxyprogesterone acetate 2.5 mg) and calcitriol + ET/HT.
Cumulative number of falls and fallers were compared between groups with 24-h urine CrCl less than 60 and 60 ml/min or greater.
Calcitriol treatment decreased the number of fallers and falls. Low CrCl less than 60 ml/min was a predictor of the number of falls per person but not fallers in the placebo group (P = 0.007). In the low CrCl group (<60 ml/min), the rate of falls decreased on calcitriol by 53% [95% confidence interval (CI) -71% to -22%; P = 0.003], calcitriol + ET/HT by 61% (95% CI -76% to -37%; P = 0.001), and ET/HT by 25% (95% CI: -55% to +24%; not significant). Calcitriol reduced the rate of falls by 30% (95% CI -49% to -4%; P = 0.027) in the CrCl 60 ml/min or greater group.
Calcitriol treatment decreases falls in all subjects but especially in elderly women with decreased renal function (<60 ml/min) and frequent fallers.
Journal of Clinical Endocrinology & Metabolism 02/2007; 92(1):51-8. · 6.50 Impact Factor
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ABSTRACT: In 487 elderly women aged 65-77 years, we examined the association of smoking with physical performance measures of muscle function and whether the effect of smoking on physical performance measures is mediated through its effect on vitamin D or estrogen metabolism.
Timed rise, timed walk at normal and fast speed, grip strength, and serum biochemical measurements were compared between smokers, past smokers, and nonsmokers. Analysis of covariance was used to compare physical performance variables while adjusting for confounding variables.
Compared to nonsmokers and past smokers, current smokers were significantly (p <.05) slower on timed rise and timed walk tests and had decreased grip strength. From multivariate analysis, smoking, age, total body fat, and serum 1,25(OH)(2)D examined as quartiles were predictors of physical performance measures. The effect of current smoking on physical performance was equivalent to a normal age-related decline in physical performance tests of 7-11 years depending on the test.
The results of this study suggest that current smoking is a risk factor for decreased muscle strength leading to decreased physical performance in elderly women. The effect of smoking on physical performance is in part mediated by its effect on 1,25(OH)(2)D metabolism. Smoking may also have an independent effect on physical performance possibly by a direct effect on muscle or through an effect on vascular function.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 02/2007; 62(1):93-100. · 4.60 Impact Factor
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ABSTRACT: Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.
Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies.
We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial.
A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation.
Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.
Journal of Bone and Mineral Research 07/2006; 21(6):855-64. · 6.37 Impact Factor
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ABSTRACT: Biochemical markers of bone turnover may reflect bone structure during anabolic treatment.
The objective was to evaluate associations between changes in biochemical markers and structural and dynamic bone parameters during teriparatide treatment.
This study was a randomized, multicenter, double-blind, placebo-controlled fracture prevention trial, with 20-month median treatment duration for biopsy subset.
The trial was conducted at 11 clinical study sites.
Sixty-one postmenopausal women with osteoporosis who had paired transiliac biopsy specimens participated in the study.
Once-daily sc injections of either placebo or teriparatide (20 or 40 microg) were administered.
The study measured: 1) serum and urinary biochemical markers of bone formation [bone alkaline phosphatase and procollagen I C-terminal propeptide (PICP)] and resorption (N-telopeptide and deoxypyridinoline); and 2) structural and dynamic analyses of bone biopsies, including two-dimensional (2D) histomorphometry and three-dimensional (3D) micro-computed tomography evaluations measured at baseline (n = 57) and 12 (n = 21) or 22 (n = 36) months.
U-N-telopeptide/creatinine and serum-PICP correlated with bone structure and dynamic indices at baseline, respectively. Changes in bone alkaline phosphatase at 1 month correlated with changes at 22 months in 2D wall thickness (r = 0.73; P = 0.001), trabecular bone volume (trabecular bone volume per total volume, BV/TV) (r = 0.58; P < 0.05), marrow star volume (r = -0.51; P = 0.05); 3D trabecular thickness (r = 0.49; P < 0.05), and BV/TV (r = 0.54; P < 0.05). Changes in PICP at 1 month correlated with changes in wall thickness (r = 0.60; P = 0.01), and 2D BV/TV (r = 0.51; P < 0.05) at 22 months. Changes in markers at 6 or 12 months were not associated with changes in structural or dynamic parameters.
Early (1-month) changes in biochemical markers of bone formation, but not resorption, correlated with improvements in bone structure after 22 months of teriparatide therapy.
Journal of Clinical Endocrinology & Metabolism 07/2005; 90(7):3970-7. · 6.50 Impact Factor
