Hasina A. Chowdhury

Overweight Postmenopausal Women Lose Bone With Moderate Weight Reduction and 1 g/day Calcium Intake

Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women. The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals. Weight reduction resulted in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day.

Calcium Supplementation Suppresses Bone Turnover During Weight Reduction in Postmenopausal Women

Bone mobilization, lowering of bone mineral density (BMD), and osteoporotic fractures are recognized in postmenopausal women with weight loss. Because a high‐calcium intake suppresses bone loss in peri‐ and postmenopausal women, the present randomized, double‐blind, placebo‐controlled study was designed to test the hypothesis that calcium supplementation prevents net bone mobilization and consequent bone mineral loss during voluntary weight reduction in obese postmenopausal women. Subjects were placed on a moderate energy‐restricted diet and either calcium supplementation (1 g/day) or placebo for 6 months. Body weight, bone turnover markers (pyridinium cross‐links), osteocalcin, and parathyroid hormone (PTH) were measured at treatment weeks 1–5, 7, 10, 13, 16, 20, and 25. Total body BMD, insulin‐like growth factor, 25‐hydroxyvitamin D, and sex hormone binding globulin (SHBG) were measured at baseline and week 25. The calcium supplemented (n = 15; age 60.9 ± 9.4 years, body mass index [BMI] 33.2 ± 4.6 kg/m2) and placebo (n = 16; age 55.8 ± 8.3 years, BMI 32.9 ± 4.5 kg/m2) groups lost similar amounts of weight over the study interval (10.2 ± 5.3% vs. 10.0 ± 5.2%) and both groups increased SHBG (p < 0.001). There was a statistical effect of calcium supplementation during weight loss to suppress pyridinium cross‐links, osteocalcin, and PTH (p < 0.05, < 0.01, and < 0.05, respectively). Loss of BMD tended to be greater in the placebo group by 1.4% (p < 0.08) after weight loss. One gram per day calcium supplementation normalizes the increased calcium–PTH axis activity and the elevated bone turnover rate observed during moderate voluntary energy restriction in postmenopausal women.

Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency.

Osteopontin null-mice were previously shown to have bones containing more mineral and larger mineral crystals. These bones were independently seen to be resistant to ovariectomy-induced remodeling. To separate the physicochemical effects of osteopontin, which is an in vitro inhibitor of mineral crystal formation and growth, from effects of osteopontin on in vivo bone remodeling, this study examined mature (5-month-old) osteopontin-null (Opn−/−) and wildtype (WT) mice given a calcium-deficient diet. Biochemical parameters were measured during 4 weeks of Ca deficiency, followed by 1 week of refeeding adequate Ca. Ca deficiency caused a transiently greater rise in bone resorption in WT than Opn−/− mice (P = 0.01), whereas only the Opn−/− mice tended to increase Ca absorption (P = 0.08), yet both groups showed elevated levels of parathyroid hormone (PTH) (P < 0.001). The rise in markers of bone formation due to Ca deficiency was similar in both groups during Ca deficiency. Fourier transform infrared microspectroscopy assessed mineral properties at 20 µm spatial resolution in different anatomic regions of the bone. The Ca-deficient Opn−/− animals had slightly increased mineral content as compared to the WT, and there was a significant increase in the mineral content of older (endosteal) bone, implying that osteoclast recruitment was impaired. Crystallinity in the Ca-deficient Opn−/− bones was increased relative to the Ca-deficient WT at all sites except adjacent to the periosteum (younger mineral). These data suggest that osteopontin has both a physicochemical effect (inhibiting crystal growth and crystal proliferation) and a role in osteoclast recruitment, and in its absence, extraskeletal organs maintain calcium homeostasis.

Urinary pyridinium cross-link excretion is increased in critically ill surgical patients.

OBJECTIVES To determine: a) the rate of pyridinium cross-links of collagen excretion, breakdown products of bone, in critically ill surgical patients in the intensive care unit (ICU); and b) the relationship between cross-link excretion and nitrogen excretion and balance to ascertain whether collagen breakdown products contribute to protein losses during a hypercatabolic state. DESIGN Observational study starting on the first postoperative day to 20 days or until discharge. SETTING A surgical ICU in a University hospital. PATIENTS Nine mechanically ventilated, postoperative surgical patients (73 +/- 3 [SD] yrs), receiving routine parenteral nutrition (18% protein) and 17 age-matched healthy subjects. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Resting energy expenditure was determined daily for < or = 5 days after admission, and energy intake was set at 1.04 times the initial energy expenditure; thereafter, values of intake were reset weekly. Daily 24-hr urine samples were analyzed for cross-links, total and urea nitrogen, calcium, and creatinine for 20 days or until discharge. Two urine samples were also analyzed for cross-links in the healthy subjects. The excretion of cross-links from the surgical patients was markedly higher (p < .001) than in the healthy subjects, and calcium balance was significantly negative (p < .05). Patients who were discharged from the ICU within 5 days showed a lower rate of cross-link excretion (p < .02) and less day-to-day variability, compared with those patients who stayed longer, whether calculated over the course of the study or over the first 2 days in the ICU. There was no correlation between cross-links and energy expenditure, nitrogen excretion, or balance. CONCLUSIONS The rate of cross-link excretion in critically ill patients: a) is markedly increased; b) is greater within the first two postoperative days in those patients who have an extended stay (> 5 days) in the ICU; and c) is independent of the rate of nitrogen excretion. These findings suggest that critically ill postoperative patients experience an acute breakdown of collagen, which is likely due to resorption of bone or possibly comes from other collagen sources.