The effect of intranasal salmon calcitonin on postmenopausal bone turnover as assessed by biochemical markers: Evidence of maximal effect after 8 weeks of continuous treatment

Although treatment with intranasal salmon calcitonin (sCT) has been shown to effectively inhibit postmenopausal bone loss, there is still controversy over both timing and the duration of its application. In an open prospective study, we therefore assessed the effect of short-term intranasal sCT on postmenopausal bone turnover, employing biochemical markers of bone metabolism. Ten early postmenopausal, previously untreated women (1–5 years after menopause) with biochemical evidence of increased bone resorption and a low bone mineral density at baseline were treated with intranasal sCT (100 IU B.I.D.) for a period of 3 months. Oral calcium (500 mg/day) was administered simultaneously, and during a further 3 month followup interval. Treatment with sCT resulted in a pronounced suppression of bone resorption markers with a maximum effect reached after 8 weeks of therapy: as compared to the respective baseline values, mean levels decreased by −26.2%±3.4% (P<0.001) for pyridinoline, −32.7%±3.5% (P<0.001) for deoxypyridinoline, −32.7%±3.3% (P<0.001) for hydroxyproline, and −24.1%±8.2% (P<0.001) for the amino-terminal telopeptide. In contrast, changes in bone formation markers of osteocalcin (−14.4%±4.8%,P<0.05) and C-terminal procollagen type I propeptide (−7.9%±3.9%, ns) were much less pronounced. Unexpectedly, after week 8 of the study all resorption markers showed a plateau and a trend to increase, although intranasal sCT was continued for a total of 12 weeks. This effect could not be attributed to the formation of anti-sCT antibodies. After cessation of treatment, both bone formation and resorption markers rapidly returned to baseline levels. Bone mineral density of both spine and hip showed no significant change during the observation period. Our results demonstrate that in postmenopausal women with a high bone turnover, intranasal treatment with 200 IU of sCT effectively reduces bone turnover and maintains bone mass, the maximum effect being reached after 8 weeks of treatment.     

Estimation of the effect of salmon calcitonin in established osteoporosis by biochemical bone markers

We reviewed data on 42 postmenopausal women with established osteoporosis (forearm fracture or a low bone mass0 who had been randomly treated for 1 year with either rectal salmon calcitonin (sCT), 100 IU daily (n=25) or nasal sCT, 200 IU daily (n=17) applying an estimation algorithm for bone loss rates. Both groups received a daily calcium supplement of 500 mg. A group of 18 age-matched women who received no treatment served as controls. The bone mineral content of the distal forearm (BMCarm) was measured every 3 months by single photon absorptiometry. The individual rates of change during the 1-year period were calculated by linear regression analysis (BMCarm). Bone loss rates were estimated initially and after 1 year of therapy by measurements of serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline and calcium (both corrected for creatinine excretion) according to the estimation algorithm. Both administration forms revealed significant control group-corrected decreases in serum and urine markers of bone turnover of 15–40% (P<0.05–0.01) and positive outcomes of 2% in BMCarm (P<0.01). The estimated effect on bone mass was expressed as the difference between the bone loss estimated after 1 year and initially (ESTBIO). A significant correlation was seen between BMCarm and ESTBIO (r=0.5, P<0.0001). We conclude that the effect of sCT on bone can be followed up by biochemical markers for bone turnover, i.e., by an annual blood and fasting urine sample, applying an estimation algorithm for the rate of bone loss.     

Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis

Summary In a 2-year study, we examined bone mass and calcium metabolism in 36 elderly women with moderate osteoporosis. The study period comprised 1 year of observation, during which the women received no treatment affecting calcium metabolism, and 1 year of treatment, during which all participants received daily salmon calcitonin (sCT) 100 IU rectally and calcium 500 mg. During the observational period a significant bone loss of 1.5% was seen in the forearm (P<0.01), whereas the spinal bone mass was virtually unchanged. After institution of treatment, the bone loss was arrested in the forearm and a significant increase of about 2% was seen in the spine (P<0.01). The net effect of treatment revealed a positive outcome in both bone compartments (1.9% and 2.9%, P<0.05–0.01). Correspondingly, the parameters of bone turnover (serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline/creatinine) did not change during the observational period, but significantly declined, 10–30%, during sCT treatment (P<0.01–0.001). Tolerance was generally good, although in one woman, anoscopy revealed irritative changes in the rectal mucosa. We conclude that, given rectally, sCT is well absorbed and well tolerated and that it has a beneficial effect on calcium metabolism in moderately osteoporotic women.     

A new biochemical marker of bone resorption for follow-up on treatment with nasal salmon calcitonin

In a double-blind, placebo-controlled, randomized group comparison, new and specific biochemical markers for bone resorption as follow-up parameters on the therapeutic response to nasal salmon calcitonin (sCT) were evaluated. Evaluation took place at an outpatient clinic where osteoporosis was being researched. The subjects included 208 women aged 68–72 treated for 2 years with either 50 IU, 100 IU, or 200 IU of nasal sCT or placebo; all groups received a daily calcium supplementation of 500 mg. Only 164 women fulfilled the study as valid completers. Markers were applied to frozen urine samples of a previously published intervention study of a new fasting urinary (fU) biochemical marker for bone resorption (CrossLaps^TM, ELISA) and the urinary excretion of cross-links (pyridinoline and deoxypyridinoline) was measured, all corrected for creatinine. Bone mineral density of the lumbar spine and rates of vertebral and peripheral fractures were measured after 2 years of treatment. The creatinine corrected urinary pyridinoline, deoxypyridinoline, and CrossLaps showed maximum decreases of 10–43% (95% confidence interval-29.5% to 9.6% and -75.1% to 9.3%;P < 0.01-0.001) after 6–9 months, after which the response leveled off. A significant difference among the four treatment groups was seen in fU CrossLaps(P < 0.01). The changes in spinal bone mass were significantly related to the decreases in fU CrossLaps: women with the highest response in spinal bone mass had decreases in fU CrossLaps of 44% (-83.5% to 7.4%) and women without response of 5% (-57.6% to 99.9%)P 0.001). In women who fractured during the 2-year period, fU CrossLaps remained unchanged, whereas decreases of 30% (-75.1% to 44.7%) were seen in women who did not fracture(P = 0.002). The results suggest that biochemical markers can be used to determine the optimum treatment regimen of nasal sCT. The response of the new marker, fU CrossLaps, significantly reflects the responses in bone mass of the spine and fracture rates.     

Bone loss during gonadotropin releasing hormone agonist treatment and use of nasal calcitonin

Gonadotropin releasing hormone (GnRH) agonists have shown to be effective in the treatment of several sex-hormone-dependent conditions. However, their use could be limited by the bone loss they induce. To evaluate the use of nasal salmon calcitonin (sCT) in preventing this bone loss, 40 patients with endometriosis were treated for 6 months with triptoreline (3.75 mg monthly) and calcium (1 g daily), and randomized in three groups — placebo, sCT 100 IU daily and sCT 200 IU daily — in a prospective double-masked study. Dual-energy X-ray absorptiometry and biochemical parameters were used to evaluate the benefit of the treatment. At baseline, there were no statistically significant differences between the groups. After 6 months, estradiol and biochemical markers of bone metabolism were at postmenopausal levels, with no difference between the groups. There was no difference in bone loss in the three groups, at all sites. Mean lumbar bone loss was 4.01±2.59% (mean±SD) in this population. In this study dosages of 100 IU and 200 IU daily of nasal sCT were insufficient to prevent bone loss during GnRH agonist treatment.     

An effective regimen of intranasal salmon calcitonin in early postmenopausal bone loss

Summary In order to devise a convenient and effective therapeutic regimen of intranasal salmon calcitonin (sCT) for the treatment of early postmenopausal bone loss, we studied the effects of a 1-year course of sCT nasal spray on vertebral mineral content (VMC), assessed by dual photon densitometry, and bone turnover in 21 early postmenopausal osteoporotic women. Subjects enrolled in the study had a value above the normal average of at least one index of bone turnover: whole body retention (WBR) of ^99mTc-methylenedichloro-bisphosphonate (^99mTc-MDP), serum bone gla protein (BGP), urinary hydroxyproline/creatinine excretion (HOP/Cr). After baseline evaluation, patients were randomized for treatment with either sCT (200 IU every other day) or plabebo. Treatment with sCT significantly increased VMC by 2.7±0.9% at 6 months, and 3.3±0.8% at 1 year, whereas a progressive decline was observed in the placebo group (-2.6±0.5%, and -3.5±0.5% after 6 and 12 months, respectively). These changes were associated with a progressive and significant reduction of all parameters of bone turnover in the sCT-treated patients, whereas no changes were detected in the control group during the study period. The differences between the two groups were significant after 1 year for VMC, BGP, and WBR (P<0.05, one-way analysis of variance). Thus, 200 IU intranasal sCT administered on alternate days is adequate to stop the fast bone loss occurring early after the menopause in women with high bone turnover rates. This therapeutical modality represents an important addition to the available pharmacologic spectrum for the prevention and treatment of postmenopausal osteoporosis.     

Effects of salmon calcitonin suppositories on bone mass and turnover in established osteoporosis

The objective of this study was to test the efficacy and safety of salmon calcitonin (sCT) suppository in postmenopausal women with previous hip fractures as an inhibitory agent of bone loss. The study was a single blind, randomized, and placebo-controlled trial comparing three parallel groups of patients. Fifty-four healthy women were randomly allocated to 1 year's treatment with either sCT 100 IU/6 times a week, 200 IU/3 times a week, or placebo/6 times a week. All groups received a calcium supplement of 500 mg daily. Fifteen patients left the study before its end, six of those due to adverse events, such as abdominal and rectal pain, nausea, headache, and diarrhea. Bone mineral density of the spine and the femoral neck was measured every 26 weeks, and biochemical markers of bone turnover were measured at baseline and week 12, 26, and 52. There were no significant changes in bone mineral density in the spine and in the hip in any of the treatment groups. No significant changes were observed in serum alkaline phosphatase, serum osteocalcin, urine hydroxyproline, and urine pyridinoline or deoxypyridinoline. Conclusively, we did not observe any significant effect on bone metabolism in women with postmenopausal osteoporosis after 1 year of treatment with sCT suppositories at the doses used.     

Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: The role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment

Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42–56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P<0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonintreated patients showed a significant increase in bone mineral content of spine and proximal forearm (P<0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group. In conclusion, our results showed that nasal salmon calcitonin administration can prevent the increased postmenorpausal bone loss in selected high bone turnover patients. The predicted annual bone loss rate, as estimated with the combination of biochemical bone markers, is useful in monitoring the responsiveness of high turnover patients to calcitonin at short intervals.     

Prevention of postmenopausal bone loss by rectal calcitonin

A group (150) of healthy women, who had been menopausal for less than 5 years and who had never received any form of treatment to prevent bone loss were entered into a randomized, controlled study comprising three arms. They were randomly allocated to the double-blind administration of five suppositories per week containing either 100 IU of salmon calcitonin or a placebo, or to a group receiving a suppository containing 200 IU of salmon calcitonin three times per week. All women received 500 mg/day of calcium supplementation. After 12 months, bone mineral density (BMD) of the spine, measured by dual energy X-ray absorptiometry, decreased significantly (P<0.01) in the placebo group by 3.1% (SD: 3.6%) but did not change in the two calcitonin groups [+1.3% (3.5%) with 100 IU/day and +2.3% (4.0%) with 200 IU 3/week]. The differences in response between the placebo group and the two calcitonin groups were significant (P<0.05), but the difference between the two regimens of calcitonin administration was not. No differences appeared among the three groups for the response at the level of the hip. Evolution of biochemical markers reflecting bone turnover did not differ significantly among groups. Nearly 40% of the women withdrew prematurely because of local (rectal or intestinal) intolerance to repetitive suppositories, with a nonsignificantly different frequency in the placebo or calcitonin groups. We conclude that rectal calcitonin might be an interesting preventive approach against trabecular postmenopausal bone loss but that long-term acceptability of suppositories should be evaluated in view of each patient's sensibility or cultural background.     

Biochemical markers of bone turnover to monitor the bone response to postmenopausal hormone replacement therapy

Hormone replacement therapy (HRT) prevents postmenopausal bone loss, and is therefore increasingly prescribed to prevent the development of postmenopausal osteoporosis. Because of individual differences in the response to HRT as well as problems with compliance, it has been debated how the skeletal response to HRT should be monitored. When estrogen production decreases at the menopause, a number of biochemical markers of bone turnover increase considerably in the order of 50%–100% from baseline. When HRT is instituted, the markers decrease again within the following 3–6 months. In the present prospective study we investigated whether the determination of biochemical markers of bone turnover may be useful for monitoring the skeletal effect of HRT. Seventy-six early postmenopausal women received HRT and 43 received placebo. The treatment period was 24 months and the women were followed with repeated bone mass measurements (every 3 months) which allowed calculation of the bone loss. Serum and urine samples were collected at 3, 6, 12 and 24 months. The placebo group lost a significant amount of bone mineral density in both the forearm and the spine (p<0.001), whereas the HRT group did not. There was, however, a relatively large overlap of values between the HRT and placebo groups, especially in the spine. After 3 months' treatment the correlation between the changes in the markers and the bone loss wasr=0.59, and this value increased tor=0.66 at 6 months andr=0.76 andr=0.77 at 12 and 24 months, respectively. The present study thus indicates that biochemical markers of bone turnover may be of value for monitoring the bone response to HRT.     

Intranasal salmon calcitonin for the prevention and treatment of postmenopausal osteoporosis

In a randomized, double-blind, placebo-controlled trial, we have studied the effects of intranasal salmon calcitonin (SCT) on bone mineral density (BMD) and biochemical markers of bone turnover over a period of 2 years. Our study comprised 117 Caucasian postmenopausal women, otherwise healthy apart from reduced bone density. They received either intranasal synthetic SCT (200 IU either three times weekly or daily) or placebo. Compared with placebo, daily intranasal calcitonin resulted in no significant bone loss in the lumbar spine, as assessed by dual photon absorptiometry, over the 2-year study period(P < 0.02). In this group, women more than 5 years postmenopause, with the lowest baseline bone mass, showed the greatest response to this treatment, with a total increase placebo in lumbar spine BMD of 3.1%. Significant spinal bone loss(P < 0.005) occurred in women receiving either placebo or thrice-weekly calcitonin. Although the rates of bone loss in the proximal femur were not significantly different in the three groups, there were differences over time. Whereas bone loss in the daily calcitonin group was insignificant, women who received placebo or thrice-weekly calcitonin experienced significant bone loss(P < 0.001). No significant changes in biochemical markers were observed in any group. Therapy was well tolerated and there were no significant treatment-related adverse events. We conclude that intranasal SCT 200 IU daily is effective and safe for the prevention of bone loss in postmenopausal women with reduced bone mass.     

The effects of salmon calcitonin-induced hypocalcemia on bone metabolism in ovariectomized rats

The ovariectomized rat has proved to be a most useful model for preclinical testing of potential therapies for osteoporosis. We describe the immediate effects of a single treatment with salmon calcitonin (sCT) on calcium homeostasis and bone turnover markers in 6-month-old sham and ovariectomized (ovx) rats at 15 days postovariectomy. Rats were fasted for 24 h prior to and following administration of 0.3 µg/kg body weight sCT. Blood specimens were collected at 0 (pretreatment), 2, 4, and 8 h. Urine samples were collected during the intervening periods. sCT treatment produced a decrease in blood ionized calcium at 2 h posttreatment in sham and ovx rats (P < 0.001), which was exaggerated in the ovx rats (P < 0.001). Increased parathyroid hormone (PTH) levels (P < 0.001) accompanied the hypocalcemia in ovx rats. Furthermore, PTH levels were significantly higher in ovx rats compared with sham rats for the same ionized calcium range of 1.275–1.300 mmol/l (P < 0.05). sCT treatment in sham rats increased urine hydroxyproline (UHyp) at 6 h posttreatment (P < 0.01). In conclusion, the calcitonin-induced hypocalcemia and secondary hyperparathyroidism was more pronounced in the ovariectomized rats, consistent with the actions of calcitonin in states of increased bone turnover induced by estrogen deficiency. This study highlights the importance of considering the actions of PTH and estrogen status when interpreting changes in calcium homeostasis and bone turnover following treatment with calcitonin in rodent models and provides further evidence for a potential role of estrogen in parathyroid function.     

Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy

This study was carried out to investigate the effectiveness and tolerability of cyclical etidronate therapy in the prevention of bone loss occurring in early postmenopausal women who are not undergoing hormone replacement therapy (HRT). A total of 109 Caucasian women aged 45–60 years were treated with etidronate 400 mg/day or placebo for 14 days followed by calcium supplementation 500 mg/day for 77 days. Ninety-one women completed the 2 years of the study. After 2 years, the estimated difference between the two groups as regards lumbar spine bone mineral density (BMD) was 2.53% (SEM 1.07%;p=0.01); BMD of the hip and wrist were not significantly different between treatment groups. A clear reduction in bone turnover was obtained as evidenced by a significant decrease in serum alkaline phosphatase level and in urinary N-telopeptide/creatinine ratio in the etidronate group; the difference between the two groups was –12%±3.2% for serum alkaline phosphatase level (p=0.019) and –22.9%+13.7% for the urinary N-telopeptide/creatinine ratio (p=0.047). There was no statistically significant difference between the two groups in terms of the serum osteocalcin levels and urinary hydroxyproline/creatinine and calcium/creatinine ratios. Etidronate was generally well tolerated and its adverse event profile was similar to that of placebo. The results of this study indicate that cyclic etidronate therapy can prevent trabecular bone loss, with no deleterious effect on cortical bone, in the first 5 years of menopause and that it has a very high safety margin.     

Effect of estrogen and calcitonin on vertebral bone density and vertebral height in osteoporotic women

Estrogen and calcitonin increase bone density of osteoporotic women, particularly on the axial skeleton. To verify whether the effect of these drugs might in part be biased by spurious increases in bone density due to radiologically irrelevant microfractures, and consequent subtle decreases in vertebral height, we followed the changes in vertebral bone density (VBD), assessed by quantitative computed tomography, in relation to vertebral height (VH) in 60 osteoporotic women. VH was measured as the sum of anterior, central and posterior heights of L1–L3 vertebral bodies on lateral radiographs. Patients received either salmon calcitonin (sCT: 50 IU subcutaneously three times per week,n=18), hormonal replacement therapy (HRT: conjugated estrogen 0.625 mg/day, days 1–25, plus medroxyprogesterone acetate 10 mg/day, days 16–25 of each month;n=21) or calcium alone (Ca: 1000 mg/day,n=21). After 1 year, VBD increased in the HRT group (+5.0 ± 1.9%,p=0.010), did not change significantly in the sCT group (+3.3 ± 2.3%,p=0.167), and decreased by 6.1 ± 1.0% (p<0.001) in the Ca group. By analysis of variance, the changes induced by HRT and sCT were significantly different from those observed in the Ca group (F=7.982,p<0.001). VH decreased slightly in all three subsets of patients (–0.9 ± 0.5% in sCT, –1.5 ± 0.3% in HRT, –0.1 ± 0.5% in Ca), but these changes were not significantly different between groups (F=2.545,p=0.081). Correcting for this height decrease by analysis of covariance did not affect the significant effect of sCT and HRT on VBD, compared with that of Ca (F=6.801,p=0.001). Furthermore, no correlation was found between changes in bone VBD and VH in any of the groups. These data indicate that microfractures do not significantly account for the increases in bone density during active treatment of osteoporosis with either estrogen or calcitonin.     

Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making. Received: 26 January 1998 / Accepted: 9 July 1998     

Can biochemical markers predict bone loss at the hip and spine?: A 4-year prospective study of 141 early postmenopausal women

A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0±3.3 years, mean menopause duration 20.4±5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at –20 °C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was –1.41% (0.18) at the lumbar spine and –0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Effect of calcitonin on bone histomorphometry and bone metabolism in rheumatoid arthritis

Summary Twenty-four women (mean age±SD 49±13 years) with classical or definite rheumatoid arthritis (disease duration 15±8 years) were treated with synthetic salmon calcitonin (SCT) nasal spray 200 IU three times a week for 3 months. Bone biopsies from the iliac crest were taken before and after SCT treatment. Histomorphometrical quantification of undecalcified bone sections was made using the manual point-counting method. SCT decreased the resorption surface of trabecular bone (ES/BS) significantly (P< 0.001). There was also a significant increase (P< 0.05) in trabecular bone volume (BV/TV) after 3 months of treatment, whereas no statistically significant changes were found in osteoid parameters. There were no significant changes in biochemical analyses of bone metabolism. We conclude that SCT might be useful in the prevention of bone loss in RA.     

Effects of 1-year treatment with ipriflavone on bone in postmenopausal women with low bone mass

Ipriflavone (IP) (7-isopropoxyisoflavone), a synthetic isoflavone derivative, is active in both inhibiting bone resorption and enhancing osteoblast function. This property suggested its clinical use in the treatment of involutional osteoporosis, and in the prevention of postmenopausal bone mass loss. Forty postmenopausal women with low bone mineral content were enrolled and randomly treated for 12 months with IP 600 mg/day or placebo (PL), according to a double-blind, parallel group design. All patients wee also given an oral calcium supplementation (1 g/day). Bone mineral density (BMD) was measured at the spine (L₂–L₄) by dual-energy X-ray absorptiometry. Bone metabolism markers (serum calcium, phosphate, osteocalcin, and alkaline phosphatase, and urinary calcium, phosphate, and hydroxyproline) were assessed at the same times. After 12 months, a reduction of BMD was evidenced in the PL-treated group, at both the spine (–2.2%, P<0.01 vs baseline) and the forearm (–1.2%). In the IP-treated group, an increase of BMD was obtained (+1.2%, P<0.01 vs placebo, at the spine; +3%, not significant, at the forearm). Bone markers were in the normal range for postmenopausal women; no statistically significant modificantions were observed during the treatment period. Three patients were withdrawn from the treatment in the IP-treated group, and two in the PL-treated group for gastrointestinal disturbances. In the other women, the tolerance of the drug was good and the complicance with the oral treatment was excellent.     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.