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Apparent failures of bone mineral density (BMD) response to teriparatide at spine or hip occur even in a high compliance context (15% spine and 55% hip). Apparent non-responders nevertheless show good biomarker response, suggesting that apparent BMD non-response is due to measurement imprecision. Calcium intake may be an important determinant of hip response.Individuals vary in response to bone active agents, but that variability is poorly quantified and its basis is not well understood. The study included 203 postmenopausal women with moderately severe osteoporosis, all treated with teriparatide, calcium, and vitamin D. The study was performed at the Creighton University Medical Center, a single site.This is a prospective study of change in bone mineral density and resorption biomarkers over a 12-month treatment period. BMD response at spine and total hip was quantified by computing slopes for each participant's values, and biomarker change by the difference in values across the 12-month study period.Of the total number of participants, 85.2% exhibited a significant spine BMD response, while only 44.8% had a significant change at the hip. However, mean biomarker response was marginally larger for the BMD non-responders at either site than for the responders, indicating biological, if not measurable densitometric, activity of teriparatide in essentially all participants.Occasional apparent failures of BMD response in patients receiving teriparatide are probably not due to failure of response at the level of the bone remodeling apparatus, but instead reflect a combination of measurement imprecision and variable bone remodeling balance. The reason for the latter remains unclear.

Intercurrent illness and episodes of hospitalization and surgery are common in an aging population, who, at the same time, are experiencing age-related bone loss. The objective was to test the hypotheses (1) that intercurrent illness severe enough to require hospitalization produces clinically important bone loss, and (2) that antiresorptive therapy will reduce that loss. The study was a retrospective analysis of bone mineral density (BMD) change at hip and spine in subjects of the risedronate postmenopausal osteoporosis phase III trials experiencing serious adverse events (SAEs). Subjects were 243 hospitalized for non-skin cancers, pneumonia, myocardial infarction, cerebrovascular accident, gallbladder disease, and pancreatitis, on whom BMD data were available both before and after the SAE; and 286 non-hospitalized control subjects matched to those with SAEs by age, height, weight, prevalent fracture, and visit interval. In hospitalized, placebo-treated participants, the annualized percent change in BMD (mean+/-SEM) across the period of hospitalization was -0.65+/-0.39 at lumbar spine, -1.13+/-0.55 at femoral neck, and -2.66+/-0.58 at femoral trochanter; the corresponding values for the non-hospitalized, placebo controls were +0.46+/-0.28, -0.77+/-0.34, and -0.67+/-0.34. These values were more negative at all three sites for the hospitalized subjects, and significantly so at lumbar spine and femoral trochanter (P=0.019 and 0.002, respectively). By contrast, in the risedronate-treated participants, all sites exhibited bone gain and there was no significant difference between hospitalized and non-hospitalized participants. Intercurrent illness resulting in hospitalization produced a rapid bone loss across the period of illness comparable in magnitude to documented age-related loss. Risedronate in a dose of 5 mg/day effectively abolished this loss.

Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.

Twenty-four hour urinary calcium was measured under controlled dietary and metabolic balance conditions in 191 normal perimenopausal women at 5-year intervals, under varying conditions of estrogen status and dietary calcium intake, generating 586 values overall. Upper and lower limits of the normal range for urinary calcium excretion are presented for the estrogen-replete and estrogen-deprived states and for varying levels of calcium intake.

Vertebral fracture prevalence and severity were analyzed by sex and age in an age-stratified proportionate sample of the enumerated population of women and men 50 years of age and older in Saunders County, Nebraska. The sample consisted of 899 women and 529 men. Of these, all but 10 women and 2 men had readable lateral spine radiographs. For both sexes, fracture prevalence rises with age. Women in their fifties have 10% vertebral fracture prevalence, and women in their eighties, 45% prevalence. Men in their fifties have 29% prevalence, and men in their eighties, 39% prevalence. The rise in prevalence and total spinal deformity with age is much greater for women than for men, but the prevalence of vertebral deformity in the fifties is much greater in men than in women.

In order to study vertebral fractures in various study populations, we earlier prepared a database of vertebral dimensions derived from spinal radiographs of 191 normal women seen regularly over 25 years. In this report we have expanded the range of measurements to include vertebral levels T3 to L5. We report means and standard deviations on anterior and posterior heights, on wedge shape and on heights relative to adjacent vertebrae. When one or both of the latter two quantities are 'far' below the mean, a vertebra is called deformed. We also describe a more flexible way of expressing damage using the number of deformed vertebrae, the degree of deformity of individual vertebrae, or the total damage to the entire spine. In assessing damage we use criteria for deformity adjusted to the limits detected by an experienced diagnostician, replacing an earlier approach based on 95% probability limits of normal variation. The normal women from whom these variations are ascertained are a low-prevalence group with respect to vertebral deformity, with prevalence of 2.8%. When the criteria developed from these women were applied to a moderate-prevalence group (37%) the model had a sensitivity of 97%, a specificity of 89% and an accuracy of 92% as regards the identification of subjects with damaged vertebrae. When used epidemiologically for a moderate-prevalence group the model has a known overestimation of 15%. the model is compared with other schemes for identifying vertebral deformities.

Both retrospectively and prospectively designed studies consistently show low bone mass and/or bone mineral content (BMC) to be risk factor for low-trauma fractures in postmenopausal women. Along with the reports of such studies there has been concern expressed that BMC measurements overlap between fracture groups, i.e., some women with high BMC develop fractures and some women with low BMC do not. In these commonly used epidemiologic study designs, BMC does not discriminate between those who have and have not experienced the untoward event at some level of the exposure factor. The ability to discriminate is more properly determined by the sensitivity and specificity of the measured value. To contrast the concepts of risk and sensitivity, a nested case-control study was conducted within a 24-year cohort study of women at risk for osteoporosis. We found that for each 1.0 decrement of BMC z-scores, the adjusted relative risk for the prospective study design was 1.67, while the odds ratio obtained from the most recent BMC z-score measurements was 1.87. A receiver operating characteristic (ROC) curve, calculated from the nested case-control study data, showed that BMC z-scores, measured after low-trauma fracture, have both low sensitivity and low specificity to detect existing fracture status.

The preferable source of calcium is a balanced diet, but medicinal supplements are sometimes necessary if patients are to reach desired intakes. A divided dose regimen (4x/d; i.e., with meals and at bedtime) results in substantially greater absorption of a supplement than does 1x/d dosing. However, differences in chemical solubility between supplement preparations are of little importance, with calcium carbonate preparations, for example, being absorbed as well or better than some much more highly soluble salts. Gastric acid is not necessary for absorption of even poorly soluble preparations, so long as they are taken with meals. Because typical patients exhibit a wide range of absorption efficiencies, it is desirable to assess absorption fraction before beginning a supplement regimen. (Some patients will need three times as large a dose as others to absorb the same amount of calcium.) Calcium intakes up to at least 62.5 mmol (2500 mg) are safe for virtually all patients.

The availability of the calcium contained in a high-calcium mineral water (Sangemini), popular in Italy, was compared in 18 healthy women with the availability of milk calcium ingested at the same calcium load, using 45Ca as the tracer in a randomized cross-over design. At an ingested calcium load of 2.5 mmol, absorption fraction averaged 0.433 for milk and 0.475 for Sangemini water. The mean quotient of the two (Sangemini/milk) was 1.129 (+/- 0.056, SEM, P < 0.05). The calcium of Sangemini water is thus highly bioavailable, and at least as bioavailable as milk calcium.