Marsha Zion

Calcium and vitamin D intake influence bone mass, but not short-term fracture risk, in Caucasian postmenopausal women from the National Osteoporosis Risk Assessment (NORA) study

SummaryThe impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women.IntroductionCalcium and vitamin D intake may be important for bone health; however, studies have produced mixed results.MethodsThe impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates.ResultsHigher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score ≤−2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. ConclusionsThus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women.

Determinants of stress fracture risk in United States Military Academy cadets.

BACKGROUND Prior studies have identified some risk factors for stress fracture in athletes and military recruits. OBJECTIVE To determine whether historical factors, physical measures, biochemical variables of skeletal metabolism, genetic factors, bone density (BMD) and bone size could predict risk of stress fracture over 4 years in physically fit cadets at the US Military Academy (USMA). METHODS Baseline surveys, assessments of height, weight, scores on the Army Physical Fitness Test, and peripheral BMD were obtained in all cadets (755 men, 136 women), and central BMD in a subset. Blood samples were analyzed for variables of calcium homeostasis, bone turnover, and selected hormones and genetic factors. Stress fractures were adjudicated by review of orthopedic notes and imaging reports. RESULTS 5.7% of male and 19.1% of female cadets had at least 1 stress fracture (58% metatarsal and 29% tibial), most within 3 months of entry to USMA. In males, risk of stress fracture was higher in those who exercised <7 h per week during the prior year (RR 2.31; CI 1.29,4.12), and in those with smaller tibial cortical area (RR 1.12; CI 1.03,1.23), lower tibial bone mineral content (RR 1.11; CI 1.03,1.20) and smaller femoral neck diameter (RR 1.35, CI 1.01, 1.81). In women, higher stress fracture risk was seen in those with shorter time since menarche (RR 1.44 per year; CI 1.19, 1.73) and smaller femoral neck diameter (RR 1.16; CI 1.01, 1.33.). CONCLUSION Although prior physical training in men, length of prior estrogen exposure in women and leg bone dimensions in both genders played a role, the maximum variance explained by all of these factors was below 10%. We conclude these factors play a minor role in the development of stress fractures in physically fit USMA cadets.

Retreatment With Teriparatide One Year After the First Teriparatide Course in Patients on Continued Long-Term Alendronate

Patients treated with teriparatide after prior and ongoing alendronate therapy experience spine BMD increases; however, some continue to be at high risk for fracture, based on persistently low BMD and/or fracture history. The objective of this study was to determine whether a second discrete retreatment course with teriparatide could produce similar biochemical and BMD changes as seen during the first teriparatide course. In the original treatment study, 126 women on alendronate for ≥1 yr were randomized to continue alendronate and receive daily teriparatide, cyclic teriparatide (3‐mo cycles), or alendronate alone for 15 mo. Of the 72 patients who completed either original teriparatide regimen, 49 completed a 12‐mo follow‐up on continued alendronate alone. At that time, 32 patients, who remained at high risk of future fracture, were recruited into the retreatment protocol and 27 completed another course of teriparatide administered daily for 15 mo (including 15 from the original daily treatment group and 12 from the original cyclic treatment group). Bone formation indices (propeptide of type I procollagen and osteocalcin) increased during both teriparatide courses with median 3‐mo increments of 120% and 72% above baseline during the original course and 60% and 40% above baseline during retreatment, respectively. Mean spine BMD increments were 6.2% after the first daily course and 4.7% after retreatment and 4.1% after the first course of cyclic teriparatide and 4.9% after retreatment. We conclude that retreatment with teriparatide stimulates bone formation and increases spine BMD to a similar extent as seen during the original teriparatide course. Retreatment with teriparatide may be a viable option for some patients with severe osteoporosis who have received prior teriparatide therapy.

Determinants of bone mass and bone size in a large cohort of physically active young adult men

The determinants of bone mineral density (BMD) at multiple sites were examined in a fit college population. Subjects were 755 males (mean age = 18.7 years) entering the United States Military Academy. A questionnaire assessed exercise frequency and milk, caffeine, and alcohol consumption and tobacco use. Academy staff measured height, weight, and fitness. Calcaneal BMD was measured by peripheral dual-energy x-ray absorptiometry (pDXA). Peripheral-quantitative computed tomography (pQCT) was used to measure tibial mineral content, circumference and cortical thickness. Spine and hip BMD were measured by DXA in a subset (n = 159). Mean BMD at all sites was approximately one standard deviation above young normal (p < 0.05). African Americans had significantly higher hip, spine and heel BMD and greater tibial mineral content and cortical thickness than Caucasians and Asians. In Caucasians (n = 653), weight was a significant determinant of BMD at every skeletal site. Prior exercise levels and milk intake positively related to bone density and size, while caffeine had a negative impact. There was an apparent interaction between milk and exercise in BMD at the heel, spine, hip and tibial mineral content and cortical thickness. Our data confirm the importance of race, body size, milk intake and duration of weekly exercise as determinants of BMD and bone size.

The influence of lifestyle, menstrual function and oral contraceptive use on bone mass and size in female military cadets

PurposeTo determine the influence of menstrual irregularity, oral contraceptive use and other factors on bone mineral density (BMD) and bone size at different skeletal sites in 135 college-aged fit women.MethodsMenstrual history, oral contraceptive use, exercise history, and nutritional factors including calcium, caffeine, and alcohol intake as well as tobacco use were determined by written survey. Height, weight and fitness levels were measured. Spine and hip BMD were measured by dual x-ray absorptiometry (DXA), calcaneus BMD by peripheral DXA, and tibial bone mineral content (BMC) and size by peripheral Quantitative Computed Tomography (p QCT).ResultsThe mean age was 18.4 ± 0.8 years. Weight and prior exercise were positively related to BMD at most skeletal sites and to tibial bone size. Milk intake was positively related to calcaneal BMD, tibial BMC and cortical thickness. Fracture history was an important predictor of spine, hip and heel BMD. Women who had ≥ 10 menstrual cycles in the year prior to BMD measurement had higher BMD at all sites as well as a greater tibial mineral content and cortical thickness than women who had oligomenorrhea/amenorrhea (≤ 9 cycles in the prior year; all p < 0.05). Oral Contraceptive (OC) users had significantly lower BMD in the spine (p < 0.02) and calcaneus (p = 0.04), smaller tibial periosteal circumference and lower tibial mineral content (p < 0.02) than non-OC users.ConclusionIn a population of fit, college-aged women, OC use and oligomenorrhea were associated with reduced BMD and bone size. Weight, as well as prior exercise and milk intake was positively related to bone density and size at some skeletal sites. Understanding these relationships would help improve skeletal health in young women.

Effect of Teriparatide on Bone Formation in the Human Femoral Neck

PURPOSE Teriparatide (TPTD) improves bone mass and microstructure resulting in reduced risk of vertebral and nonvertebral fractures. However, hip bone mineral density improvements are modest and there are no data confirming that TPTD reduces hip fracture risk. To study the effects of TPTD on the proximal femur, we performed a double-blind trial of TPTD vs placebo (PBO) in patients with osteoarthritis from whom femoral neck (FN) samples were obtained at total hip replacement (THR) surgery. METHODS Participants were randomly assigned to receive TPTD or PBO for an average of 40 days before THR. Double tetracycline labeling was initiated 21 days prior to THR to allow histomorphometric assessment of bone formation. During the THR, an intact sample of the FN was procured, fixed, and sectioned transversely. Serum levels of bone turnover markers were measured at baseline and during the THR. Standard histomorphometric parameters were measured and calculated on four bone envelopes (cancellous, endocortical, intracortical, and periosteal). The primary outcome measure was bone formation rate/bone surface (BFR/BS). RESULTS Forty individuals were enrolled (25 women, mean age, 71.5 ± 8.0 y and 15 men, mean age, 68.9 ± 7.7 y). In cancellous and endocortical envelopes, BFR/BS was 100% higher in the TPTD vs PBO group (P < .05). Bone turnover markers measured at the time of THR correlated with BFR/BS. CONCLUSIONS TPTD stimulates bone formation rapidly in cancellous and endocortical envelopes of the FN. Our findings provide a mechanistic basis for TPTD-mediated improvement in FN bone mass and ultimately hip strength. This study is the first demonstration of the effect of any osteoporosis medication on osteoblast activity in the human proximal femur.

Daily or Cyclical Teriparatide Treatment in Women With Osteoporosis on no Prior Therapy and Women on Alendronate.

CONTEXT Intermittent 3-month cyclic administration might optimize the anabolic potential of teriparatide (TPTD). OBJECTIVE To determine whether 3-month cyclical TPTD would produce a similar bone mineral density (BMD) response to daily therapy in treatment naive (Rx-naive) women and to confirm the results in alendronate (ALN)-treated (ALN-Rx) women over 24 months. DESIGN Subjects participated in a randomized open-label study for 2 years. SETTING Osteoporosis clinical research center. PARTICIPANTS A total of 150 postmenopausal women with osteoporosis in two cohorts: 86 Rx-naive and 64 ALN-Rx. INTERVENTION Within cohorts, women were randomized to daily TPTD for 24 months or four 3-month TPTD cycles, each followed by 3 months off (12 mo total TPTD). MAIN OUTCOMES BMD at 24 months. RESULTS In Rx-naive women, BMD increased in the lumbar spine (LS), total hip (TH), trochanter (Troch), and femoral neck (FN) in daily and cyclic groups (within groups, P < .0002, except cyclic FN, P = .13). Increases were 2-fold greater in daily vs cyclic groups (LS, 8.8 vs 4.8%; TH, 4.0 vs 2.1%; Troch, 5.6 vs 3.1%; and FN, 2.9 vs 1.2%; group differences, all P < .05). In daily vs cyclic groups, radius BMD declined (-4.2 vs -2.1%, respectively; both P < .01; group difference, P = .08) and total bone mineral increased modestly (1.4%, P = .18; vs 1.5%, P = .06; group difference, not significant). In ALN-Rx women, there were no group differences (daily vs cyclic: LS, 7.5 and 6.0%; TH, 3 and 2.5%; Troch, 3.7 and 3.3%; FN, 3 and 1.5%; within groups, P < .003; except cyclic FN, P = .2). In daily and cyclic groups, radius BMD decreased (-0.7% [not significant] and -1.4% [P < .05], respectively), and total bone mineral increased 2.3 and 3% (both P < .001). CONCLUSION Cyclic TPTD over 2 years improves BMD similarly to daily treatment in women who remain on ALN, despite only 50% of the TPTD dose. However, there does not appear to be a BMD advantage to cyclic administration in treatment-naive women for up to 24 months.

Evaluation of continuous summary physical performance scores (CSPPS) in an elderly cohort

Background and aims: Physical performance is an important predictor of quality of life among the elderly. A valid and sensitive measure of physical performance is needed in order to evaluate possible interventions. The aim of this study was to examine the validity and reliability of the Continuous Summary Physical Performance Score (CSPPS) and its relationship to the Quartile Summary Physical Performance Score (QSPPS). Methods: This cross-sectional study of an elderly cohort from 5 centers in the US and Europe included men and women (>age 65) reporting at least two domains of disability. Subjects completed assessments of mobility and ability to perform activities of daily living (ADLs), the physical component of the SF-36, and a self-rating of physical performance. Timed physical performance tests were used to calculate the CSPPS and QSPPS. Results: 216 subjects took part (mean age=81 years). The distribution of CSPPS scores was similar for men and women, with a mean of 59.2 (SD 17.8), median of 64.3, and range from 1.3 to 91. Subjects with older age, higher degree of disability, and lower self-rated physical performance had lower CSPPS scores. The CSPPS had good test-retest reliability (r=0.92), and CSPPS and QSPPS are highly correlated (r=0.94, p<0.001). However, the QSPPS appears to lack the linearity, and the ranges of the CSPPS for each score of the QSPPS overlap substantially. Conclusions: In a cohort with moderate to severe disability, the CSPPS appears to be a valid, reproducible measure that can discriminate smaller yet clinically meaningful differences in physical function, as compared with the QSPPS.

The clinically meaningful change in physical performance scores in an elderly cohort.

Background and aims: The aim of this study was to assess annual changes in the continuous summary physical performance score (CSPPS) and the quartile summary physical performance (QSPPS) score, evaluate how these changes relate to self-reported changes in physical function and to examine clinically meaningful changes in CSPPS and QSPPS. Methods: This was a longitudinal study of an elderly cohort of men and women (age >65) reporting at least two domains of disability from 5 centers in the US and Europe. Subjects completed assessments of mobility, ability to perform activities of daily living (ADLs), and the physical component of the SF-36 at both baseline and at 1-year, as well as a self-report of change in function over the year. Timed physical performance tests including walking speed, repeated chair stands and balance were used to calculate QSPPS and CSPPS at baseline and one year. Results: Regardless of the tool used to evaluate clinical significance (ADL, SF-36 PF, mobility disability, self-rating of physical performance) or a determination of the small meaningful change estimates based on effect size, it appears that a change of ∼3 points in the CSPPS or 0.6 points in the QSPPS is clinically meaningful. Conclusion: In this cohort with moderate to severe disability, an annual change of approximately 3 points in CSPPS and 0.6 points in QSPPS are clinically meaningful and these changes are evident at one year.

Eating disorders, menstrual dysfunction, weight change and DMPA use predict bone density change in college-aged women

INTRODUCTION There are limited longitudinal studies that have evaluated bone mineral density (BMD) changes in college-aged women. Our objective was to simultaneously evaluate factors influencing 4-year BMD change. METHODS This was a longitudinal cohort study of healthy, physically active women in the US Military Academy (n=91; average age=18.4years). Assessments over four years included: height, weight, calcium intake, physical fitness, menstrual function (annual number cycles), oral contraceptives (OCs) or depot-medroxyprogesterone acetate (DMPA) use, and eating disorder behavior (Eating Disorder Inventory; (EDI)). BMD was measured annually at the lumbar spine and total hip by dual X-ray absorptiometry and calcaneal BMD by PIXI. Slope of 4year BMD change at each skeletal site (spine total hip and calcaneus) was calculated for each woman. RESULTS BMD gains occurred at the spine in 50% and the hip in 36% of women. In unadjusted analyses, spine bone gain was positively related to menstrual cycle frequency (p=0.04). Spine and hip BMD loss occurred in those using DMPA (p<0.01) and those with the highest EDI quartile scores (p<0.05). BMD change was unrelated to OC use. Hip and calcaneus BMD decreased with weight loss (average 4.8+2.2lb/year) as compared to those with stable weight/weight gain (p<0.05). In multivariable analysis, spine BMD increase was significantly related to African American (AA) race, normal EDI score and normal menses. Hip BMD increase was related to AA race, weight increase and normal menses. DMPA use was associated with spine, hip, and calcaneus bone loss. CONCLUSION On average, BMD may modestly increase in college-aged women, in the absence of risk factors. However, risk factors including subclinical eating disorders, weight loss, menstrual dysfunction and DMPA use can have significant detrimental effects on BMD in young healthy physically active women.