Calcium Supplementation Suppresses Bone Resorption in Early Postmenopausal Women

In order to establish whether calcium supplementation suppresses bone resorption in early postmenopausal women and whether any response is related to calcium absorption status, we studied 22 healthy women (median age 52 years) all within 5 years of the menopause. Urine was collected between 9.00 p.m. and 9.00 a.m., and 9.00 a.m. and 9.00 p.m., (2 days) and a fasting blood and spot urine sample was obtained at 9 a.m. On the first day, 5 μCi of ⁴⁵Ca in 250 ml water with 20 mg calcium carrier as the chloride was given at 9.00 a.m. and a further blood sample was obtained at 10.00 a.m. to measure calcium absorption. A 1 g calcium load was given at 9.00 p.m., immediately before the second 24-hour urine collection. There was a rise in plasma ionized calcium (1.18 ± 0.010 mmol/liter versus 1.21 ± 0.011 mmol/liter, P < 0.01) and a fall in plasma PTH (4.2 ± 0.34 pmol/liter versus 3.5 ± 0.31 pmol/liter, P < 0.01) from baseline after the calcium load, and a trend for the magnitude of the change in PTH to be inversely related to calcium absorption (r =−0.33, P= 0.13). In the fasting spot urine samples, there were falls in hydroxyproline (OHPr/Cr; 14.6 ± 0.71 versus 12.6 ± 0.83, P < 0.001), pyridinoline (Pyr/Cr; 75 ± 2.8 versus 70 ± 3.5, P < 0.05), and deoxypyridinoline (Dpd/Cr; 22.7 ± 1.2 versus 19.5 ± 1.1, P < 0.005) after the calcium load. The calcium load suppressed urinary Dpd/Cr between 9.00 p.m. and 9.00 a.m. (P < 0.005), but not between 9.00 a.m. and 9.00 p.m. We conclude that acute administration of a 1 g calcium load suppresses bone resorption in early postmenopausal women, probably by decreasing PTH secretion. Received: 2 December 1996 / Accepted: 21 May 1997     

Comparison of the Absorption of Calcium Carbonate and Calcium Citrate after Roux-en-Y Gastric Bypass

Introduction  Roux-en-Y gastric bypass (RYGB) restricts food intake. Consequently, patients consume less calcium. In addition, food no longer passes through the duodenum, the main site of calcium absorption. Therefore, calcium absorption is significantly impaired. The goal of this study is to compare two common calcium supplements in gastric bypass patients. Method  Nineteen patients were enrolled in a randomized, double-blinded, crossover study comparing the absorption of calcium from calcium carbonate and calcium citrate salts. Serum and urine calcium levels were assessed for peak values (C _max) and cumulative calcium increment (area under the curve [AUC]). Serum PTH was assessed for minimum values (PTH_min) and cumulative PTH decrement (AUC). Statistical analysis was performed using a repeated analysis of variance model. Results  Eighteen subjects completed the study. Calcium citrate resulted in a significantly higher serum C _max (9.4 + 0.4 mg/dl vs. 9.2 + 0.3 mg/dl, p = 0.02) and serum AUC (55 + 2 mg/dl vs. 54 + 2 mg/dl, p = 0.02). Calcium citrate resulted in a significantly lower PTH_min (24 + 11 pg/ml vs. 30 + 13 pg/ml, p = 0.01) and a higher AUC (−32 + 51 pg/ml vs. −3 + 56 pg/ml, p = 0.04). There was a non-significant trend for higher urinary AUC in the calcium citrate group (76.13 + 36.39 mg/6 h vs. 66.04 + 40.82, p = 0.17). Conclusion  Calcium citrate has superior bioavailability than calcium carbonate in RYGB patients.     

Diminished Acute Response of Osteoclasts to Calcium Load in Thyroidectomized Patients

To elucidate the role of endogenous calcitonin (CT) in the regulation of bone resorption, we evaluated the acute effects of an intravenous calcium load in nine patients after total thyroidectomy (aged 29.2 ± 8 years) compared with nine healthy subjects. After overnight fasting, intravenous infusions of elemental calcium 1.7 mg/kg body weight were given over a 10-minute period. Blood samples for measurements of serum ionized calcium (S-iCa), plasma intact CT, parathyroid hormone (PTH), and plasma type I collagen cross-linked C-terminal telopeptide (-CTX) were obtained 3 minutes before and at 13, 30, 60, 90, and 150 minutes after the start of the infusion. At baseline, parameters of calcium and bone metabolism were similar in both groups. A similar increase in S-iCa and decrease in plasma PTH levels were observed in both groups. However, the plasma CT increased significantly by 13 minutes (P < 0.05) and -CTX decreased significantly as early as 30 minutes (P < 0.05) (decrease by 36% as compared with the baseline) only in the group consisting of healthy individuals. In the thyroidectomized group, the plasma -CTX did not decrease significantly during the first 60 minutes (decrease by only 8% as compared with the baseline) and response to the calcium load was significantly diminished throughout the study period as compared with that of the healthy subjects (P < 0.01). In conclusion, the results indicate that the increased CT secretion is responsible for the rapid initial decrease in the bone resorption following an acute intravenous calcium load.     

Inhibition of Bone Resorption by Divided-Dose Calcium Supplementation in Early Postmenopausal Women

We have previously shown that a calcium (Ca) supplement of 1000 mg given in the evening reduces the overnight and early morning, but not the daytime, excretion of bone resorption markers in postmenopausal women within five years of the menopause. In the present study, we have looked at the effect of splitting the Ca into two doses of 500 mg each given in the morning and evening. We studied 19 healthy women (median age 53 years) who were all within 5 years of the menopause. On the 2 study days, urine was collected from 9 a.m. to 9 p.m. (day collection), and from 9 p.m. to 9 a.m. (night collection); a further fasting (spot) urine sample was obtained at 9 a.m. at the end of the night collection. The first day was a control day; on the second day the subjects ingested 500 mg Ca as the carbonate at 9 a.m. and 9 p.m. We measured pyridinoline cross-links excretion in all the samples, as well as hydroxyproline in the fasting urine. The Ca supplements lowered urinary excretion of the markers during the day (P < 0.01), had only a marginal effect during the night, but reduced excretion significantly in the fasting urine (P < 0.001). In the whole 24-hour period, the falls in resorption markers were small but comparable to those seen after the ingestion of 1 g of Ca in the evening. We conclude that the acute administration of 0.5 g Ca in the morning and evening reduced the markers of bone resorption in early postmenopausal women during the day but not during the following night, whereas the single 1 g supplement had the reverse effect. Over the 24-hour period, there was nothing to choose between the two regimes. Women at this stage in their life cycle probably require a larger Ca supplement if they are not taking estrogen. Received: 5 April 2000 / Accepted: 27 July 2000 / Online publication: 2 November 2000     

Acute Effects of 2 Hours of Moderate-Intensity Cycling on Serum Parathyroid Hormone and Calcium

Previous studies have found that serum parathyroid hormone (PTH) increases in response to relatively short (<60 minutes), intense bouts of exercise, possibly as a result of decreases in serum calcium. Whether longer, less intense exercise also stimulates an increase in PTH is not known. The effects of 2 hours of moderate-intensity cycling on serum PTH and calcium were investigated in 20 competitive male cyclists, aged 22–45 years. Serum concentrations of PTH and calcium were measured before and after exercise. Dermal calcium loss was estimated using patch collections and loss of sweat. There were increases in PTH from 40.6 ± 15.6 to 69.5 ± 25.5 pg/mL (P < 0.001) and in serum calcium from 9.3 ± 0.3 to 9.6 ± 0.5 mg/dL (mean ± standard deviation, P = 0.001) in response to exercise. Contraction of plasma volume explained the rise in calcium but not PTH. Dermal calcium loss was estimated at 138.0 ± 71.9 mg for the 2-hour exercise bout. Neither the change in serum calcium nor the dermal calcium loss was significantly related to the increase in PTH. The study demonstrated that prolonged exercise stimulates PTH secretion. The effects of such transient increases in PTH on bone metabolism are not known.     

Comparison of Serum and Urine Assays for Biochemical Markers of Bone Resorption in Postmenopausal Women with and without Hormone Replacement Therapy and in Men

Biochemical markers of bone resorption have been used to characterize metabolic bone disease and assess therapeutic response. Most studies have used the urinary measurement of collagen crosslinks, but serum assays have recently been developed that may have less analytic and biologic variability. In the present study, we measured urine and serum N- and C-terminal crosslinked telopeptides of type I collagen (NTX and CTX) and serum bone sialoprotein (BSP) in postmenopausal women with or without hormone replacement therapy (HRT) and in men of similar age. In these populations, the variability of serum and urine markers was similar, except that serum NTX showed somewhat lower variability in postmenopausal women. Urine and serum assays correlated well with one another and were significantly lower in postmenopausal women on HRT compared with untreated women. The difference in women on HRT was similar for sNTX, uNTX and BSP (35–40%) and greater for sCTX and uCTX (52–53%). There was an inverse correlation between markers and bone mineral density, largely attributable to the high correlation in women not on HRT. Fractional excretion of NTX and CTX were estimated at 0.20 ± 0.07 and 0.44 ± 0.11, respectively. These values were independent of the concentration of the marker or of creatinine in the urine. We conclude that serum markers are useful measures of bone resorption in these populations, in whom the use of such markers is likely to be helpful in the management of osteoporosis. Received: 23 August 1999 / Accepted: 30 November 1999     

Association Study of Parathyroid Hormone Gene Polymorphism and Bone Mineral Density in Japanese Postmenopausal Women

Association of BST B1 restriction fragment length polymorphism (RFLP) of the parathyroid hormone (PTH) gene with bone mineral density (BMD) was examined in 383 healthy postmenopausal women in Japan who were unrelated. The RFLP was represented as B or b, the capital letter signifying the presence of and the small letter the absence of restriction site for BST B1. The frequency of each genotype—BB, Bb, and bb—was 82.5%, 16.7%, and 0.8%, respectively. When we statistically compared age, years after menopause, body height, and body weight between the BB genotype and the Bb genotype groups, there was no significant difference between the groups. However, the lumbar BMD and the score of BMD adjusted for age and body weight (Z score) were significantly lower in the group of genotype Bb than in the BB: 0.859 ± 0.019 g/cm² versus 0.925 ± 0.011 (mean ± SE, P= 0.01) and −0.412 ± 0.138 versus 0.067 ± 0.082 (mean ± SE, P= 0.01). In addition, the Z score of total body BMD in the Bb genotype group was lower than that in the BB group. Comparison of serum and urinary biochemical bone metabolic markers suggested that the subjects with Bb genotype might be in a relatively higher state of bone turnover than those with BB genotype. These results suggest that the polymorphism in the PTH gene would be a useful genetic marker for lower BMD and the susceptibility for osteoporosis. Received: 19 March 1998 / Accepted: 24 June 1998     

Absorption of Calcium as the Carbonate and Citrate Salts, with Some Observations on Method

Calcium supplement use has increased and there is confusion about the relative absorbability of various sources. Absorbability of calcium from the carbonate and citrate salts was compared at 300 mg and 1000 mg calcium loads, ingested as part of a light breakfast meal. Absorption was measured at the high load both by tracer appearance in serum and by the absorptive increment in urinary calcium, and at the low load by the tracer method only. Subjects were 37 healthy adult men and women, studied as outpatients, and each tested on both salts at the same load. Mean tracer absorption (± SD) for both salts combined was 36.0% at the 300 mg load and 28.4% at the 1000 mg load. In both experiments the observed mean difference in absorption between salts was very small. By the tracer method the within-subject difference (carbonate less citrate) was +3.3%± 1.2% of the ingested dose (mean ± SEM; P <0.05) at the high load, and at the low load, 3.6%± 2.7% (NS). Combining the two experiments yielded zero difference between sources. By the urinary calcium increment method, the mean difference between salts at the 1000 mg load was 1.8 ± 4.1 mg (NS). Side-by-side comparisons of the two methods revealed that the tracer method was 3 times more sensitive than the urinary increment method. We conclude that, when taken with food, calcium from the carbonate salt is fully as absorbable as from the citrate, and that the urinary increment method is not sufficiently sensitive to be useful in comparing sources in free-living subjects. Received: 6 April 1998 / Accepted: 6 April 1998     

Increase of Bone Resorption and the Parathyroid Hormone in Postmenopausal Women in the Long-term after Roux-en-Y Gastric Bypass

Background  The effects of Roux-en-Y Gastric Bypass (RYGB) on bone in the long-term remains unclear. We assessed bone metabolism and bone mineral density (BMD) 1 to 5 years after RYGB. Methods  We designed a retrospective cohort study in 26 postmenopausal women (58.0 ± 3.9 years old) with RYGB 3.5 ± 1.1 years before (body mass index (BMI) 29.5 ± 3.8 kg/m², presurgery 43.6 ± 5.5 kg/m²) and 26 nonoperated women (57.5 ± 4.7 years old, BMI 29.2 ± 4.1 kg/m²) matched by age and BMI. The main measures were BMD, serum carboxy telopeptide (CTx), total alkaline phosphatases (ALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and ghrelin. Results  RYGB group, compared to nonoperated women, had higher CTx (0.71 ± 0.21 vs. 0.43 ± 0.15 ng/ml; P < 0.01) and PTH (68.3 ± 35 vs. 49.4 ± 16 pg/ml; P = 0.02). There were no differences between RYGB and nonoperated women in: calcium and vitamin D intake (759 ± 457 vs. 705 ± 460 mg/day; 176 ± 160 vs. 111 ± 86 UI/day), ghrelin (763 ± 336 vs. 621 ± 274 pg/ml), ALP (101 ± 22 vs. 94 ± 25 UI/l), 25OHD (18.8  ± 7.6 vs. 17.4 ± 5.9 ng/ml), lumbar spine BMD (1.059 ± 0.32 vs. 1.071 ± 0.207 g/cm²), or femoral neck BMD (0.892 ± 0.109 vs. 0.934 ± 1.1 g/cm²). Conclusions  RYGB is associated to high bone resorption and hyperparathyroidism prevalence in postmenopausal women in the long-term. This occurs independently of the intake of calcium, vitamin D status, or ghrelin and does not seem to affect BMD after RYGB.     

Comparison of Hypotensive Response following Intravenous Injection of Parathyroid Hormone 1-84 and 1-34 in Conscious Rats

Activation of parathyroid hormone 1 (PTH-1) receptors on vascular smooth muscle cells causes relaxation and decreases blood pressure in rats and humans. However, when PTH(1-84) and PTH(1-34) were injected in anesthetized rats, PTH(1-34) produced a greater decrease in blood pressure. This study quantified the dose-response relationship of the hypotensive response to intravenously injected PTH(1-84) and PTH(1-34) in conscious rats and assessed the role that the C-terminal region of PTH(1-84) played in the differences. Mean arterial pressure (MAP) decreased rapidly following injection of both peptides (0–100 nmol/kg) and reached a nadir at 1–2 minutes before increasing at a rate that was dose- and time-dependent. PTH(1-34) produced a greater hypotensive effect than PTH(1-84) at most doses tested and was significantly different from PTH(1-84) at 1–10 nmol/kg. The greatest difference in MAP decrease between PTH(1-84) and PTH(1-34) (24 and 35 mm Hg, respectively) occurred at 10 nmol/kg. Median effective dose (ED₅₀) values for PTH(1–84) and PTH(1-34) were significantly different (5.9 and 1.3 nmol/kg, respectively). The C-terminal PTH fragments PTH(7–84), PTH(39–84), and PTH(53–84) did not affect MAP when injected alone (10 nmol/kg), nor did they influence the hypotensive response when given at a 10–fold molar excess in combination with PTH(1-84) or PTH(1-34) (1.4 nmol/kg). In conclusion, PTH(1-84) is a less potent but, because it induced the same maximum response, not a less efficacious hypotensive agent than PTH(1-34) when administered by bolus intravenous injection in conscious rats. We found no evidence to support the concept that the C-terminal region of PTH is responsible for this difference in potency.     

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.     

Effects of Race on Diurnal Patterns of Renal Conservation of Calcium and Bone Resorption in Premenopausal Women

Previous studies showed differences in bone and mineral metabolism in African-Americans and Caucasians: reductions in serum 25-hydroxyvitamin D [25(OH)D], urinary calcium and skeletal remodeling and moderate secondary hyperparathyroidism. Diurnal studies were carried out in 7 African-American and 7 white normal premenopausal women matched for age, weight and height to further characterize these racial differences in calcium homeostasis. Serum 25(OH)D was significantly lower and serum intact parathyroid hormone (PTH) was significantly higher in the African-American compared with the white women, whereas serum total calcium, Ca²⁺, phosphorus and 1,25-dihydroxyvitamin D [1,25(OH)₂D] were not different in the two groups. Serum intact PTH increased significantly at night in the white women and did not change in the African-American women. Urinary calcium was 47% lower in the African-American than in the white women during the day but was not different at night. Urinary calcium declined at night by 53% in the white women and by 40% in the African-American women. Stepwise multivariate analysis showed that determinants of urinary calcium were mean 24 h serum intact PTH and serum Ca²⁺ in the two groups together, mean 24 h serum intact PTH, body mass index (BMI) and serum 25(OH)D in the white women, and BMI in the African-American women. Urinary N-telopeptide of type I collagen, a marker of bone resorption, increased by over 60% at night in both groups and was 25% lower in African-American compared with white women, but the difference was not statistically different. Urinary free deoxypyridinoline also increased at night in both groups and was not racially different. Thus, African-American women show higher serum intact PTH and greater conservation of calcium than white women throughout the day. In both groups, maintenance of serum calcium at night is achieved by increased bone resorption and renal conservation of calcium. Received: 15 April 1999 / Accepted: 6 July 1999     

Acute Effects of Different Phosphorus Sources on Calcium and Bone Metabolism in Young Women: A Whole-Foods Approach

The recommended dietary phosphorus intake is exceeded in the typical Western diet. However, few studies have been conducted on the bioavailability and metabolic consequences of dietary phosphorus from different food sources. In this study, acute effects of dietary phosphorus from three different food sources and a phosphate supplement on calcium and bone metabolism were investigated. Sixteen healthy women aged 20–30 years were randomized to five controlled 24-hour study sessions, each subject serving as her own control. At the control session, calcium intake was ca. 250 mg and phosphorus intake ca. 500 mg. During the other four sessions, phosphorus intake was about 1,500 mg, 1,000 mg of which was obtained from meat, cheese, whole grains, or a phosphate supplement, respectively. The foods served were exactly the same during the phosphorus sessions and the control session; only phosphorus sources varied. Markers of calcium and bone metabolism were followed. Analysis of variance with repeated measures was used to compare the study sessions. Only the phosphate supplement increased serum parathyroid hormone (S-PTH) concentration compared with the control session (P = 0.031). Relative to the control session, meat increased markers of both bone formation (P = 0.045) and bone resorption (P = 0.049). Cheese decreased S-PTH (P = 0.0001) and bone resorption (P = 0.008). These data suggest that the metabolic response was different for different foods.     

Effect of Direction and Rate of Change of Calcium on Parathyroid Hormone Secretion in Uraemia

We have studied the control of amino-terminal parathyroid hormone(PTH) secretion in haemodialysis patients in response to slowor fast calcium infusion and during acute hypocalcaemia. Innine patients, fast calcium infusion (0.4 mmol/kg bodyweightper hour) for 15 min increased ionised calcium and reduced PTH,with an initial t of 12.8 min. After the infusion had ceased,calcium decreased steadily, and PTH increased, mean PTH reachingbaseline values when calcium was still significantly greaterthan pre-infusion values. During slow calcium infusion for 2.5h (0.1 mmol/kg bodyweight per hour), parathyroid suppressionwas evident at 15 min, when the calcium increment was only 0.03mM. After 60 min, PTH did not decrease further despite progressivehypercalcaemia. Hypocalcaemic haemodialysis led to rapid increasesin PTH. After 15 min, the mean calcium decrement was 0.09 mM(P<0.01) and the mean PTH increment was 283 pg/ml (P<0.01).The parathyroid response was maximal at 30 min, and did notincrease subsequently, despite progressive hypocalcaemia fora further 90 min. During recovery from hypocalcaemia, PTH reducedand, despite comparable hypocalcaemia, PTH during periods ofincreasing calcium was always lower at a given calcium concentrationthan while calcium was decreasing. This influence of the directionof change of calcium was not seen during hypocalcaemia. Theresults showed that even in advanced renal disease, the parathyroidglands are highly responsive to small initial increments (0.03mM) and decrements (0.09 mM) in blood calcium, though less soto further perturbation of blood calcium. During hypocalcaemia,the parathyroid glands respond to both the absolute value ofblood calcium and also to the direction of change of calcium.     

Acute Suppression of Bone Turnover With Calcium Infusion in Persons With Spinal Cord Injury

Background:

Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism.

Objective:

To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI.

Study Design:

Case series.

Subjects:

Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D ≤20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion.

Methods:

Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH.

Results:

All results are expressed as means (± SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 ± 3.5 ng/mL (range: 10.2–19.6 ng/mL); PTH, 70 ± 25 pg/mL (range: 37–100 pg/mL); and NTx, 21 ± 7 nM bone collagen equivalents (BCE) (range: 14–34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 ± 0.2 to 10.8 ± 0.9, 10.5 ± 0.8, and 10.6 ± 0.6 mg/d; PTH was suppressed from 70 ± 25 pg/mL to 18 ± 12, 16 ± 9, and 15 ± 9 pg/mL, respectively; NTx fell from 21 ± 8 nM BCE to 17 ± 5, 12 ± 4, and 12 ± 3 nM BCE, respectively.

Conclusions:

Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.     

The Association between Parathyroid Hormone, Vitamin D and Bone Mineral Density in 70-Year-Old Icelandic Women

Parathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64° N), where daily intake of cod liver oil is common and mean calcium intake is high. ln PTH correlated inversely with 25(OH)D (r=−0.26, p<0.01). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R ²= 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis. Received: 3 January 2000 / Accepted: 10 April 2000     

Suppression of Bone Resorption in Early Postmenopausal Women by Intranasal Salmon Calcitonin in Relation to Dosage and Basal Bone Turnover

In the present study, we assessed the ability of increasing doses of intranasal calcitonin to suppress urinary deoxypyridinoline cross-link (DPD), a specific biochemical marker of bone resorption, in early postmenopausal women. Subjects consisted of 30 healthy Thai women within 5 years of postmenopause, randomly assigned to 50, 100, or 200 IU of intranasal calcitonin 5 days/week for 3 months. Calcium supplementation by calcium carbonate capsules at 750 mg of elemental calcium per day was given to all subjects. Twenty four-hour urine for DPD and creatinine assays was collected at baseline, 1 month, and 3 months after treatment. All DPD values were corrected with urinary creatinine before analyses. Data were expressed as mean ± SEM. DPD decreased significantly 1 month after intranasal calcitonin treatment (P < 0.01). However, at 3 months, DPD increased when compared with the values at 1 month (P < 0.01), suggesting that there may be a reduction in the suppression of bone resorption after prolonged calcitonin therapy. Using a stepwise multiple regression model to address whether dosage and DPD at baseline influence the response to intranasal calcitonin, it was found that DPD suppression after intranasal calcitonin was not related to dosage but was strongly associated with baseline DPD (P < 0.0001). Suppression of bone resorption in early postmenopausal women by intranasal calcitonin is determined more by the state of bone turnover at baseline than the dosage of calcitonin. Received: 10 March 1997 / Accepted: 14 November 1997     

Role of Parathyroid Hormone in Bone Fragility of Postmenopausal Women with Vitamin D Insufficiency

Vitamin D insufficiency is related to an increase in PTH, which might be critical for an increase in bone fragility. However, the role of endogenous PTH in vitamin D insufficiency-induced fracture risk remains unclear. The present study was performed to examine the relationships among vitamin D insufficiency, bone fragility, and PTH in 202 Japanese postmenopausal women. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured. The percentages of subjects with 25(OH)D levels below 10, 15, and 20 ng/ml were 5.0, 41.0, and 80.7%, respectively. Serum 25(OH)D levels were negatively related to age and serum levels of Cr and PTH; they were positively related to bone mineral density (BMD). In multiple regression analysis, BMD was significantly related to 25(OH)D levels when adjusted for age, body mass index (BMI), and serum levels of Cr and PTH. Multiple logistic regression analysis showed that lower 25(OH)D levels were significantly related to prevalent fracture risk when adjusted for age, BMI, serum levels of Cr and PTH, as well as femoral neck BMD. The proportion of subjects with prevalent fractures was significantly higher in the group with lower PTH and lower 25(OH)D than in the group with lower PTH and higher 25(OH)D or higher PTH and higher 25(OH)D. In conclusion, vitamin D insufficiency was found to be related to prevalent fracture risk independently of PTH. Functional hypoparathyroidism, rather than functional hyperparathyroidism, might be a risk factor for bone fragility in vitamin D insufficiency.