We assessed the associations of eight bone turnover markers (BTMs) with baseline and 1-year percentage changes in lumbar spine and hip bone mineral density (BMD) of 293 postmenopausal women undergoing treatment with hormone replacement therapy (HRT) or placebo using squared correlation coefficients (R 2 ). In 239 women assigned to treatment with estrogen alone or with with estrogen plus progestins (active treatment), mean percentage changes for all markers decreased significantly and remained below baseline values through 3 years of study, whereas mean percentage changes for 54 women assigned to the placebo group showed no significant change from baseline in any marker. At baseline, age and body mass index (BMI) together accounted for 16% and 25% of the variance in spine and hip BMD, respectively. The telopeptide resorption marker, cross-linked N-telopeptide of type I collagen (NTX), alone accounted for 12% and 8% of variance, respectively. Another telopeptide, carboxyterminal telopeptide of type I collagen (Crosslaps), accounted for 8% and 7% of variance, respectively. A bonespecific alkaline phosphatase (BALP-2) accounted for 8% of variance at the spine and 5% at the hip. No other marker accounted for more than 5% of total variance at either site; adding either baseline NTX, Crosslaps, or BAP-2 to regressions containing age and BMI increased R 2 values at the spine and hip to about 22% and 28%, respectively. In the placebo group, baseline spine BMD accounted for 4% of the variance in 1-year spine BMD percentage change, whereas baseline values for age and BMI accounted for 1% and 0% of the variance, respectively; none of the three accounted for more than 0% of hip BMD percentage change; Crosslaps and NTX contributed 5% and 4% to the variance in 1-year spine BMD percentage change, but other markers accounted for < 2% of variance at the spine. At the hip, another BALP (BALP-1) accounted for 4% of variance, but no other baseline marker except NTX accounted for more than 1% of variance. In the active treatment group, baseline values for age, BMI, and spine BMD together accounted for 13% of the percentage change in spine BMD and for 4% of the BMD change at the hip. No individual or pair of baseline markers significantly enhanced these R 2 values, but addition of 1-year percentage changes in some individual markers did significantly increase it. The largest R relationships between quartile and change in spine BMD, and these did not reach significance at the hip. When the 1-year change in markers was stratified into quartiles, significant relationships with percentage change in spine BMD were observed only for BALP phosphatases. We conclude that BTMs are not a surrogate for BMD to identify women with low bone mass and that they offer little useful information for predicting BMD changes for individual untreated or HRT-treated postmenopausal women. (J Bone Miner Res 1999;14:1583-1595)

No abstract

We assessed the cross-sectional relationship of age, menopausal years, body mass, previous estrogen use, and ethnic background to bone mineral status in a sample of 875 healthy postmenopausal women at the time they were recruited from the community to participate in a multicenter clinical trial. The women were 1-10 years postmenopause, 45-64 years of age, and had not received estrogen replacement therapy within 3 months of enrollment. Of the participants, 89% were white, 69% had a spontaneous menopause, and 53% had a history of previous estrogen replacement therapy. Bone mineral density (BMD) of the lumbar spine (L2-4) and proximal femur was measured by dual-energy x-ray absorptiometry. Results were consistent with a significant negative linear regression of BMD on age or years from menopause. Body mass index (BMI) correlated significantly with BMD at all sites (L 2-4 r = 0.28; femoral neck r = 0.34, p < 0.0001). BMD adjusted for age and BMI were higher at both sites in women who had taken estrogen versus those who had not (L2-4 0.976 +/- 0.009 versus 0.932 +/- 0.01; femoral neck 0.740 +/- 0.006 versus 0.708 +/- 0.008, p < 0.05). Adjusted BMD also increased with duration of ERT. Parity was negatively associated with L2-4 BMD (p = 0.03) but did not correlate significantly with BMD at the femoral neck. Black women had the highest L2-4 BMD, and Hispanic women had the highest femoral neck BMD, even when results were adjusted for age and BMI. When data were corrected for differences in bone size, these interethnic differences were no longer significant. We conclude that increased body mass is positively correlated with BMD, and this may confer a degree of skeletal protection to heavier postmenopausal women. Exposure for 5 years to exogenous estrogen is associated with significantly increased age- and BMI-adjusted BMD.

Background and Purpose: Lateral ankle sprain the most common injury in physically active populations. Individuals who sustain an acute lateral ankle sprain may not receive timely formal rehabilitation and are at an increased risk to have subsequent sprains which can lead to chronic pain and instability. Attention to essential factors for ligament protection and healing while preserving ankle movement, may result in a more stable yet mobile ankle offering improved outcomes. The purpose of this case series was to describe the methods and observe the outcomes associated with a comprehensive strategy for managing acute first episode grade II lateral ankle sprains. Study design: Prospective case series. Case Descriptions and Interventions: Ten patients (mean age 26.7 years, range 16-51 years, mean 2.3 days from injury) with acute grade II lateral ankle sprain were treated with an approach to protect the injured ligament, prevent impairments to movement, restore strength and proprioception, and progress to full function. Patient outcomes were assessed at four, eight and 12 weeks. Follow-up interviews at six and 12 months assessed injury recurrence. Outcomes: Patients were treated for an average of eight sessions over a mean of seven weeks. Rapid change in selfreported function, ankle ROM, and pain were observed in the first four weeks of care. Clinically meaningful improvements in function and ankle ROM were also noted at eight weeks and maintained at 12-week follow-ups. All patients returned to desired physical activity with only a single re-sprain event within one year after injury. Conclusion: The results of this prospective case series suggest that a treatment approach designed to protect the injured ligament, maintain and restore normal ankle motion, and provide a tailored functional pathway to return to run and sport demonstrated resolution of symptoms and improvement in reported functional outcomes in a group of patients following grade II acute primary ankle sprain.