Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

Self-reported calcium use in a cohort of postmenopausal women receiving osteoporosis therapy: results from POSSIBLE US™.

UNLABELLED: Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%). INTRODUCTION: Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. METHODS: Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. RESULTS: At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. CONCLUSIONS: Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

Daily treatment of aged ovariectomized rats with human parathyroid hormone (1-84) for 12 months reverses bone loss and enhances trabecular and cortical bone strength.

Most studies that have investigated the anabolic effects of parathyroid hormone (1-84) (PTH) or PTH fragments on the skeleton of ovariectomized (OVX) rats have evaluated the short-term effects of high-dose PTH(1-34) in young animals. This study used densitometry, histomorphometry, and biomechanical testing to evaluate the effects of 12-month daily treatment with low-dose PTH (15 or 30 microg/kg) in rats that were 10 months old at baseline, 4 months after OVX. Bone mineral density (BMD) and bone strength were reduced substantially in control OVX rats. The 15 microg/kg dose of PTH restored BMD to levels similar to those in sham animals within 6 months at the lumbar spine, distal and central femur, and whole body and maintained the BMD gain from 6 to 12 months. The 30 microg/kg dose produced greater effects. Both PTH doses normalized the trabecular bone volume-to-total volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia (where baseline BV/TV was very low), solely by increasing trabecular thickness. PTH dose-dependently increased bone formation by increasing the mineralizing surface, but only the 30 microg/kg dose increased resorption. PTH increased cortical BMD, area, and thickness, primarily by increasing endocortical bone formation, and restored all measures of bone strength to levels similar to those in sham animals at all skeletal sites. PTH increased bone mass safely; there was no osteoid accumulation, mineralization defect, or marrow fibrosis and there were no abnormal cells. Thus, long-term PTH therapy normalized bone strength in the aged OVX rat, a model of postmenopausal osteoporosis, through increased bone turnover and enhanced formation of both trabecular and cortical bone.

Insufficiently dosed intravenous ibandronate injections are associated with suboptimal antifracture efficacy in postmenopausal osteoporosis.

Less frequent bisphosphonate dosing in women with postmenopausal osteoporosis has the potential to promote therapy adherence through improved convenience. Ibandronate is a highly potent nitrogen-containing bisphosphonate, proven to significantly increase vertebral and nonvertebral bone mineral density (BMD) when administered as a convenient intravenous injection. A recent double-blind, placebo-controlled, randomized phase III study explored the antifracture efficacy and safety of 1 and 0.5 mg iv ibandronate injections, given once every 3 months, in 2862 women (55-76 years) with postmenopausal osteoporosis [one to four prevalent vertebral fractures and lumbar spine (L1-L4) BMD T score of less than -2.0 and greater than -5.0 in >or=1 vertebra]. All participants received daily vitamin D (400 IU) and calcium (500 mg) supplementation. The primary endpoint was the incidence of new morphometric vertebral fractures after 3 years. However, although a consistent trend toward a reduction in the incidence of new morphometric vertebral fracture was observed in the active treatment arms compared with placebo (9.2% vs. 8.7% vs. 10.7% in the 1 mg, 0.5 mg and placebo groups, respectively), as well as in the incidence of nonvertebral and hip fractures, the magnitude of fracture reduction was suboptimal and was insufficient to achieve statistical significance. At the studied doses, intravenous ibandronate injections also produced dose-dependent, but comparatively small, increases in lumbar spine BMD (4.0% and 2.9%, respectively) and decreases in biochemical markers of bone resorption and formation, relative to placebo. Optimal fracture efficacy likely requires more substantial increases in BMD and more pronounced suppression of bone turnover. In light of the clear dose-response relationship observed in this and other studies, this is likely to be achieved with higher intravenous doses of ibandronate. The results of a recent phase II/III study (Intermittent Regimen Intravenous Ibandronate Study: the IRIS study) provide support for this hypothesis.

Intermittent intravenous administration of the bisphosphonate ibandronate prevents bone loss and maintains bone strength and quality in ovariectomized cynomolgus monkeys.

Using a clinically relevant regimen, this study investigated the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, biochemical markers of bone turnover, densitometry, histomorphometry, biomechanical properties, and bone concentration in aged ovariectomized monkeys. Sixty-six female cynomolgus monkeys, aged 9 years and older, were ovariectomized (OVX) or sham operated. Intravenous (iv) bolus injections of ibandronate at 10, 30, or 150 microg/kg or placebo were administered at 30-day intervals (corresponding to intervals of 3 months in humans), starting at OVX, for 16 months. OVX significantly decreased bone mass at the lumbar spine, proximal femur, femoral neck, and radius and increased bone turnover in a time-dependent manner, as assessed by dual energy X-ray absorptiometry, peripheral quantitative computed tomography, or histomorphometry. Ibandronate iv bolus injections administered at 30 microg/kg every 30 days prevented osteopenia induced by estrogen depletion. OVX-induced increases in bone turnover (as determined by activation frequency, bone formation rate, and biochemical markers of bone turnover, including urinary N-telopeptide and deoxypyridinoline excretion and serum values for osteocalcin and bone-specific alkaline phosphatase) were suppressed on treatment, and bone mass, architecture, and strength were preserved at clinically relevant sites. Treatment with high-dose (150 microg/kg/dose) iv bolus injections of ibandronate further increased bone mass and improved bone strength at both the spine and femoral neck, without adversely affecting bone quality. In contrast, treatment with a 10 microg/kg/dose only partially prevented the OVX-induced effects. These data support the potential for the long-term administration of ibandronate by intermittent iv bolus injections in humans to prevent osteoporosis and improve bone quality at clinically relevant sites.

Effects of nicotine on bone mass and strength in aged female rats.

This study investigated the effects of nicotine on bone mass and biomechanical properties in aged, estrogen-replete (sham-operated) and estrogen-deplete (ovariectomized) female rats. Eight month old, retired breeder, sham-operated and ovariectomized Sprague-Dawley rats were left untreated for 12 weeks to establish cancellous osteopenia in the ovariectomized group. The animals were then administered saline, low dose nicotine (6.0 mg/kg/day) or high dose nicotine (9.0 mg/kg/day) via osmotic minipumps for 12 weeks. Vertebrae and femora were collected at necropsy for determination of bone mass and strength. As expected, ovariectomy had a negative effect on most endpoints evaluated. Vertebral body bone mineral content (BMC) and density (BMD) and the structural (ultimate load and yield load) and material (ultimate stress, yield stress, and flexural modulus of elasticity) strength properties were lower in the OVX rats than in the sham-operated rats. Femoral diaphysis BMC, BMD, ultimate load, and flexural modulus were also lower in the OVX rats than in the sham-operated rats. The nicotine doses administered resulted in serum nicotine levels that averaged 1.5-4.5-fold greater than those observed in heavy smokers. Despite the high doses used, nicotine had no effect on vertebral BMC, BMD, or any of the structural and material strength properties in either the OVX or the Sham rats. In addition, nicotine had no effect on femoral diaphysis BMC, BMD, ultimate load, stiffness, ultimate stress, or flexural modulus. Femoral yield load and stress were lower in low dose nicotine-treated rats than in vehicle-treated rats. However, differences were not detected between the high dose nicotine- and vehicle-treated rats for either femoral yield load or stress. The results suggest that tobacco agents other than nicotine are responsible for the decreased bone density and increased fracture risk as observed in smokers.

Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group.

The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.

Calcium intake and body weight.

Five clinical studies of calcium intake, designed with a primary skeletal end point, were reevaluated to explore associations between calcium intake and body weight. All subjects were women, clustered in three main age groups: 3rd, 5th, and 8th decades. Total sample size was 780. Four of the studies were observational; two were cross-sectional, in which body mass index was regressed against entry level calcium intake; and two were longitudinal, in which change in weight over time was regressed against calcium intake. One study was a double-blind, placebo-controlled, randomized trial of calcium supplementation, in which change in weight during the course of study was evaluated as a function of treatment status. Significant negative associations between calcium intake and weight were found for all three age groups, and the odds ratio for being overweight (body mass index, >26) was 2.25 for young women in the lower half of the calcium intakes of their respective study groups (P: < 0.02). Relative to placebo, the calcium-treated subjects in the controlled trial exhibited a significant weight loss across nearly 4 yr of observation. Estimates of the relationship indicate that a 1000-mg calcium intake difference is associated with an 8-kg difference in mean body weight and that calcium intake explains approximately 3% of the variance in body weight.

The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial.

BACKGROUND: Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women. OBJECTIVE: To determine the bone-sparing effect of continuous low-dose HRT in elderly women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University osteoporosis research and clinical center. PATIENTS: 128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less. INTERVENTION: Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups. MEASUREMENTS: Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months. RESULTS: During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived. CONCLUSIONS: Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.

Correcting calcium nutritional deficiency prevents spine fractures in elderly women.

We tested the spine antifracture and bone sparing efficacy of 1.2 g/day of oral calcium as carbonate in two groups of elderly women, one with prevalent fractures (PF, n = 94) on entry and the other without (NPF, n = 103). It was a prospective randomized, double-blind, placebo-controlled trial in mostly rural communities in women over age 60 who were living independently and were consuming < 1 g/day of calcium. We obtained annual lateral spine radiographs and semiannual forearm bone density over 4.3 +/- 1.1 years and determined vertebral fractures by radiographic morphometry augmented by physician assessment. In the PF group, 15 of 53 subjects on calcium had incident fractures, compared with 21 of 41 on placebo (p = 0.023, chi2). Calcium did not reduce the rate of incident fractures in the NPF group. Those with a prevalent fracture on entry and not treated with calcium were 2.8 times more likely to experience an incident fracture than all others. Change in the forearm bone mass on placebo in the PF group was -1.24 +/- 2.41%/year compared with +0.31 +/- 1.80%/year on calcium (p < 0.001). In the NPF group, the difference was less: -0.39 +/- 2.08%/year versus 0.00 +/- 1.64%/year (p = 0.2). We conclude that in elderly postmenopausal women with spine fractures and selfselected calcium intakes of < 1 g/day, a calcium supplement of 1.2 g/day reduces the incidence of spine fractures and halts measurable bone loss.

Mechanical loading stimulates rapid changes in periosteal gene expression.

Although mechanical forces regulate bone mass and morphology, little is known about the signals involved in that regulation. External force application increases periosteal bone formation by increasing surface activation and formation rate. In this study, the early tibial periosteal response to external loads was compared between loaded and nonloaded contralateral tibia by examining the results of blot hybridization analyses of total RNA. To study the impact of external load on gene expression, RNA blots were sequentially hybridized to cDNAs encoding the protooncogene c-fos, cytoskeletal protein beta-actin, bone matrix proteins alkaline phosphatase (ALP), osteopontin (Op), and osteocalcin (Oc), and growth factors insulin-like growth factor I (IGF-I) and transforming growth factor-beta (TGF-beta). The rapid yet transient increase in levels of c-fos mRNA seen within 2 hours after load application indirectly suggests that the initial periosteal response to mechanical loading is cell proliferation. This is also supported by the concomitant decline in levels of mRNAs encoding bone matrix proteins ALP, Op, and Oc, which are typically produced by mature osteoblasts. Another early periosteal response to mechanical load appeared to be the rapid induction of growth factor synthesis as TGF-beta and IGF-I mRNA levels were increased in the loaded limb with peak levels being observed 4 hours after loading. These data indicate that the acute periosteal response to external mechanical loading was a change in the pattern of gene expression which may signal cell proliferation. The altered pattern of gene expression observed in the present study supports previous evidence of increased periosteal cell proliferation seen both in vivo and in vitro following mechanical loading.

Determinants of endogenous fecal calcium in healthy women.

Endogenous fecal calcium (EFC) excretion was measured in 518 studies in 191 normal perimenopausal women, most studied two to three times over a 15 year period. EFC averaged 102 +/- 25 mg/day. Absorption fraction was simultaneously determined by both double-isotope and balance methods. EFC was found to vary inversely with absorption fraction, and the observed relationship was used to calculate the total amount of calcium (TIC) entering the gut from endogenous sources. TIC averaged 140 +/- 34 mg/day and was found to be correlated with a number of intake and body size variables. Phosphorus intake was the most strongly correlated of all the variables (r = 0.404; P < 0.0001), each increment of 0.1 g phosphorus intake being associated with an increase in TIC of 6 mg. Lean body mass was the best correlated of the body size variables, with TIC rising by 1.6 mg/day for every kg lean mass. There were also small but significant correlations with protein and energy intakes, the latter suggesting that some of the variation of TIC is related to the amount of food consumed. Caffeine, previously reported as elevating TIC, did not exhibit a significant relationship in this study.

Prevention of osteoporosis: calcium nutrition.

Calcium is a threshold nutrient which means that a nutritional response in terms of calcium balance or bone mass will be present at intakes below the threshold and not above. The analogy can be made with the case of iron nutrition and anemia. Estimates of the threshold intake levels can be made for all stages of life based on available calcium balance data. They range between 1.3 g/day for infants to 1.5 g/day for women past menopause. Calcium nutrition is most important during growth and development in achieving genetically programmed peak skeletal mass. It is also important in maintaining bone mass in the elderly years. Calcium needs are supplied by the breakdown of the skeleton during the first few years after menopause, and thus calcium nutrition is less important until about 5 or 6 years after cessation of menses. Optimum calcium intake is best obtained from food sources; however, the lower food intake of modern humans compared with the food intake of humans during involution has resulted in difficulty in gaining an adequate intake of calcium. Calcium supplements are destined to become and important source of dietary calcium and thus some attention must be paid to their nutritional value. Solubility of a calcium salt is not a major determinant of absorbability over a range of 5 orders of magnitude of solubility. However, there is a well-defined enhancing effect of the co-ingestion of a meal with calcium supplements. It would seem prudent to recommend that any calcium supplement be given at meal times.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term consistency of nutrient intakes in humans.

Consistency of intake over time for calcium, phosphorus, protein and energy, as estimated from diet diaries, was studied prospectively in two groups of women. One group provided short-term data (n = 165), and the other, data spanning intervals of up to 20 y (n = 164). Although group average intakes changed little, there was a great deal of individual variation. Even at intervals as short as 6 m, current intake estimates accounted for only about 40% of the variance of intakes at an earlier time. Over longer intervals, the predictive value of one estimate in respect to a second deteriorated even further. Thus, across 5 y, less than 25% of the variance of all four nutrient intakes could be accounted for by current intake. The 95% confidence interval for an estimate of earlier intake based upon a later measurement was more than +/- 700 mg for calcium, the least consistent nutrient. The other three nutrients showed nearly identical interstudy consistency, with uncertainties relative to their respective means being about half as large as for calcium. These data show that accurate longitudinal estimates of intake require continuous, prospective monitoring and that current intake is not a good estimator of past intake for most nutrients, especially for calcium.

Absorbability of calcium sources: the limited role of solubility.

Fractional absorption of seven chemically defined calcium sources was measured in normal adult women under standardized load conditions. Solubility of the sources in water at neutral pH ranged from a low of 0.04 mM to a high of 1500 mM. The relationship of solubility to absorbability was weak. In the range from 0.1 to 10 mM, within which most calcium supplement sources fall, there was no detectable effect of solubility on absorption. Data from four food sources are presented for comparison. Absorbability of food calcium was not clearly related to absorbability of the dominant chemical form in the food concerned. These findings suggests that (1) even under controlled, chemically defined conditions, solubility of a source has very little influence on its absorbability; and (2) absorbability of calcium from food sources is determined mainly by other food components.

Histomorphometric effects of calcium or calcium plus 25-hydroxyvitamin D3 therapy in senile osteoporosis.

To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis, we studied a group of 39 women aged 69 +/- 7 (standard deviation, SD) years with severe osteoporosis. The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis. No subject had risk factors for osteopenia other than their age and postmenopausal status, and no subject was receiving therapy for bone disease at the onset of the study. Subjects were followed for 2 years after randomization to receive either 1200 mg/day of calcium (as calcium carbonate) and 40 micrograms/day of 25-OHD (calcium-25-OHD group), or 1200 mg/day of calcium plus placebo (calcium-placebo group). Calcium-25-OHD resulted in a clear increase in 25-OHD levels (p less than 0.001) and an increase in calcium absorption as indicated by urinary calcium excretion. Nevertheless, there was no significant change in fasting serum calcium, phosphorus, alkaline phosphatase, PTH, or 1,25-(OH)2D in either group. Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period. Unexpectedly, repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups, presumably as a result of the calcium supplementation alone. In summary, calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia. The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium supplements: anion effects.

The effects on bone remodeling of two anions commonly associated with calcium in the food and supplement chain (carbonate and phosphate) were evaluated in a pilot study in eight normal premenopausal women. Each woman was studied twice under full metabolic balance controls, once before starting treatment and then a second time after 4 months of treatment with either sodium bicarbonate in a dose providing 3240 mg carbonate daily or a mixture of sodium and potassium phosphates, providing 1144 mg additional phosphorus daily. Intakes of calcium and protein remained approximately constant between studies. Remodeling was measured by paired studies of both whole body calcium kinetics and trans-ilial bone biopsies. The extra phosphate was almost completely absorbed and produced the expected decline in urine calcium. Both anions were associated with slight decreases in intestinal calcium absorption efficiency; however neither anion altered bone remodeling as measured either by radiocalcium kinetics or by histomorphometry. Since the anion doses we used were larger than the average woman is likely to receive from either food or supplement sources, we conclude that neither anion alters bone remodeling in humans to a clinically significant degree. Additionally these findings underscore the essential safety of increased phosphorus intakes and have relevance to the use of phosphate as a remodeling activator in the ADFR (coherence therapy) approach to treatment of osteoporosis.

Aluminum does not accumulate in teenagers and adults on prolonged parenteral nutrition containing free amino acids.

Prolonged total parenteral nutrition (TPN) with solutions containing hydrolyzed casein has been associated with aluminum accumulation in patients with bone disease. We investigated the effects of free amino acids in TPN solution on plasma, urine, and bone aluminum in six patients, five of whom had symptoms of bone disease or documented demineralization. No evidence of aluminum accumulation was found. TPN with free amino acids, containing 42 micrograms aluminum per liter or less, does not lead to aluminum loading in adolescents or adults.

Calcium absorption and achlorhydria.

Defective absorption of calcium has been thought to exist in patients with achlorhydria. I compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement.

The effect of milk supplements on calcium metabolism, bone metabolism and calcium balance.

Twenty-two healthy postmenopausal women were divided into two groups, one group of 13 received milk supplementation of 24 oz per day and the other group of 9 controls received no intervention during two years of observation. Extensive inpatient metabolic balance and radiocalcium kinetic studies were performed at the beginning and at the end of one year of observation. In the milk supplement group, fractional calcium absorption (x +/- SD) decreased from .243 +/- .058 to .176 +/- .058, absorbed calcium increased from .159 +/- .052 gm/d to .248 +/- .063 gm/d, urine calcium increased from .117 +/- .034 gm/d to .146 +/- .027 gm/d, bone accretion decreased from .385 +/- .079 gm/d to .326 +/- .063 gm/d, bone resorption decreased from .446 +/- .098 gm/d to .342 +/- .106 gm/d and endogenous fecal calcium increased from .105 +/- .023 gm/d to .120 +/- .021 gm/d. All these changes were significant within the group and the mean changes were significantly different from the mean changes observed in the control group. Calcium balance in the milk supplemented group improved from -.061 +/- .056 gm/d to -.017 gm/d +/- .073 gm/d. Predicted changes in calcium and bone metabolism held true except that the suppression of bone remodeling was less than previously found using calcium carbonate supplements. We conclude that milk and milk products can be recommended as sources of calcium, that data on the effects of increasing calcium intake from other sources can be applied to milk and that milk may offer an advantage because it does not suppress bone remodeling as severely as calcium carbonate.