During pregnancy, the mother adapts to meet the calcium demands of the fetus. The effect of this adaptation on the maternal skeleton is not fully understood. Our objectives were to evaluate changes in bone mineral density (BMD) and bone turnover during pregnancy. We studied 16 women longitudinally, with baseline measurements before pregnancy; then at 16, 26, and 36 weeks of pregnancy; and postpartum. We measured total-body BMD and biochemical markers of bone resorption (urinary pyridinium crosslinks and telopeptides of type I collagen) and bone formation (serum bone alkaline phosphatase, propeptides of type I procollagen [PINP] and osteocalcin). We also measured parathyroid hormone (PTH), insulin-like growth factor I (IGF-I), and human placental lactogen. Postpartum, BMD increased in the arms (2.8%, P F 0.01) and legs (1.9%, P F 0.01) but decreased in the pelvis (؊3.2%, P F0.

Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

Biochemical markers of bone turnover (bone turnover markers, BTMs) can be used to study changes in bone remodelling in osteoporosis. Investigators and clinicians should be aware of the appropriate sample collection and storage conditions for optimum measurements of these markers. Improvements in the variability of BTM measurements have resulted from the development of assays for automated analysers, and from international consensus regarding their use. Appropriate reference intervals should be used for the optimum interpretation of results. BTMs can provide information that is useful for the management of patients with osteoporosis, for both the initial clinical assessment and for guiding and monitoring of treatment. BTMs are clinically useful to determine possible causes of secondary osteoporosis by identifying patients with high bone turnover and rapid bone loss. In the follow-up of treatment response, BTM levels respond rapidly to both anabolic and antiresorptive treatments. BTM changes can also be used for understanding the mechanism of action of drugs in development and identifying the correct dose; they are also potentially useful as surrogate biomarkers for fracture.

Biochemical markers of bone turnover may be useful to monitor patients taking hormone replacement therapy (HRT). The aim of this study was to assess the utility of markers in monitoring HRT by comparing the response of a large panel of markers to HRT with their within subject variability. We measured the response of markers to transdermal estradiol in 11 postmenopausal women over 24 weeks. We measured the within subject variability of markers in 11 untreated healthy postmenopausal women over the same period. The mean decrease in markers of bone formation after 24 weeks treatment ranged from 19% for procollagen type I C-terminal propeptide (PICP) to 40% for procollagen type I N-terminal propeptide (PINP). The mean decrease in markers of bone resorption ranged from 10% for tartrate-resistant acid phosphatase (TRAP) to 67% for C-terminal cross-linked telopeptide. The least significant change (LSC at p < 0.05), calculated from the within subject variability in the untreated group, was used to define response. LSC for osteocalcin was 21%, bone alkaline phosphatase 28%, PICP 24%, PINP 21%, type I collagen telopeptide 28%, TRAP 17%, urinary calcium 90%, hydroxyproline 75%, total deoxypyridinoline 47%, free pyridinoline 36%, free deoxypyridinoline 26%, N-terminal cross-linked telopeptide 70%, and C-terminal cross-linked telopeptide 132%. The greatest number of responders after 24 weeks of treatment were found using PINP and osteocalcin (9 each), and free deoxypyridinoline (8 each) and total deoxypyridinoline (7 each). Lumbar spine bone mineral density defined four patients as responders. The ability to detect a response differs between markers and is not dependent on the magnitude of response to therapy. (J Bone Miner Res 1998; 13:1124-1133)

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Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3 We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status.

Introduction: Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers.Methods: Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53-84 years), randomized to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for two years. The LSC for each marker was derived within the study population whereas RIs were obtained from a control group of healthy premenopausal women (age 35-40 years).Results: Over 70% of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI -63% (difference 13%, 95%CI 0 to 27.1, P=0.049) and good compliance -67% (difference 15.9%, 95%CI 6.3 to 25.5, P=0.001). Responders had a greater increase in spine bone density compared to non-responders; for example 6.2% vs. 2.3%, (difference 3.9%, 95%CI 1.6 to 6.3, p=0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate.Conclusions: Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.Key words: postmenopausal osteoporosis, bone turnover markers, variability, bisphosphonate Mini Abstract (50 words)We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis.Response was more likely with alendronate and ibandronate, than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80% of her medication.