Long-Term (3 Years) Prevention of Trabecular Postmenopausal Bone Loss with Low-Dose Intermittent Nasal Salmon Calcitonin

in Journal of Bone and Mineral Research : The Official Journal of the American Society for Bone and Mineral Research (1994), 9(1), 69-73

The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group ... [more ▼]

The long-term effect of intermittent low-dose nasal salmon calcitonin on trabecular early postmenopausal bone loss was assessed as follow-up to a previously published study. Randomized controlled group comparison was made of 287 healthy women with 6-36 months of natural menopause and no treatment interfering with calcium metabolism at an outpatient clinic for research in bone and cartilage metabolism. The 287 women were randomly allocated to 3 years of treatment with either 500 mg/day, 5 days/week of calcium or the same amount of calcium plus 50 IU/day, 5 days per week of nasal salmon calcitonin. A total of 186 women complied with the study protocol throughout. The main outcome measures were bone mineral density of the lumbar spine (DPA) and biochemical parameters reflecting bone turnover (serum alkaline phosphatases, urinary calcium/creatinine, and hydroxyproline/creatinine ratio). The average changes in bone mineral density after 36 months showed a positive (p < 0.05) outcome (1.8 +/- 5.7%; mean +/- SD) in the group treated with salmon calcitonin and calcium and a significant (p < 0.01) loss (-5.8 +/- 4.8%) in patients receiving calcium alone. The difference between the evolution of the two groups was significantly (p < 0.01) different after 6 months of treatment and remained so until the end of the study. No significant changes were recorded in biochemical parameters reflecting bone turnover. As previously shown during a 1 year follow-up, nasal salmon calcitonin given at low dose and intermittently, in association with calcium, can counteract trabecular postmenopausal bone loss. [less ▲]

Acute Biochemical Variations Induced by Four Different Calcium Salts in Healthy Male Volunteers

in Osteoporosis International : A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis & the National Osteoporosis Foundation of the USA (1993), 3

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non ... [more ▼]

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Paget's Disease of Bone Treated with a Five Day Course of Oral Tiludronate

in Annals of the Rheumatic Diseases (1993), 52(1), 54-7

Chloro-4-phenyl thiomethylene bisphosphonate (tiludronate) is a new drug which can be used as an inhibitor of bone resorption. As it remains in bone for a long time, and as mineralisation defects have ... [more ▼]

Chloro-4-phenyl thiomethylene bisphosphonate (tiludronate) is a new drug which can be used as an inhibitor of bone resorption. As it remains in bone for a long time, and as mineralisation defects have only been seen at doses much higher than those required to decrease osteoclastic activity, it could be given at high doses over a short period of time. Eighteen patients with Paget's disease of bone were randomly allocated to three therapeutic groups receiving respectively 600, 800, and 1200 mg/day tiludronate for five days. Serum alkaline phosphatase activity and the urinary hydroxyproline/creatinine ratio were quickly and drastically reduced in all three groups. A significant reduction of serum alkaline phosphatases and the hydroxyproline/creatinine ratio was still present six months after the five day therapeutic course, reflecting a sustained activity of tiludronate even after stopping treatment. Dose dependent short and long term reductions of bone turnover rate were observed. Biochemical assessment of haematological, renal, or hepatic tolerance did not show any toxicity of tiludronate. Fifty per cent of patients treated by a dose of 1200 mg/day reported gastrointestinal disturbances, however, making this dosage unsuitable for clinical practice. [less ▲]

Calcitonin Metabolism in Senile (Type II) Osteoporosis

in Osteoporosis International : A Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis & the National Osteoporosis Foundation of the USA (1992), 2

The exact role of calcitonin (CT) in the pathogenesis of senile (Type II) osteoporosis remains unknown. Whole plasma calcitonin (iCT) and extracted monomeric calcitonin (eCT) basal levels, metabolic ... [more ▼]

The exact role of calcitonin (CT) in the pathogenesis of senile (Type II) osteoporosis remains unknown. Whole plasma calcitonin (iCT) and extracted monomeric calcitonin (eCT) basal levels, metabolic clearance rate (MCR) and production rate (PR) of iCT and eCT were measured in 41 postmenopausal women, including 14 hip fractures (OP II) and 27 healthy controls. No significant difference appeared for basal iCT levels between OP II (mean +/- SEM: 41.9 +/- 3.4 pg/ml) and controls (mean +/- SEM: 46.2 +/- 5 pg/ml). eCT basal levels were similar in OP II (mean +/- SEM: 5.42 +/- 0.5 pg/ml) and in controls (mean +/- SEM: 7.3 +/- 0.7 pg/ml). MCR were similar in the two groups. iCT PR were similar in OP II (mean +/- SEM: 17.2 +/- 1.5 micrograms/24 h) and controls (mean +/- SEM: 18.6 +/- 1.1 micrograms/24 h). No difference appeared between eCT PR in OP II (mean +/- SEM: 2.3 +/- 0.2 micrograms/24 h) and controls (mean +/- SEM: 3.2 +/- 0.3 pg/ml). From these data, no evidence appears that calcitonin might be one of the determinant factors in the pathogenesis of senile osteoporosis. [less ▲]

Dual Photon Absorptiometry of Lumbar Spine in West European (Belgian) Postmenopausal Females: Normal Range and Fracture Threshold

in Clinical Rheumatology (1990), 9(2), 220-4

Bone mineral content (BMC) and bone mineral density (BMD) of lumbar spine have been measured in 695 healthy postmenopausal and 64 type I osteoporotic Belgian, Caucasian females. Bone loss is strongly ... [more ▼]

Bone mineral content (BMC) and bone mineral density (BMD) of lumbar spine have been measured in 695 healthy postmenopausal and 64 type I osteoporotic Belgian, Caucasian females. Bone loss is strongly correlated to time elapse from menopause (Tm) with a maximum rate of bone loss during the first five years of menopause. BMC (gHA) = 461 + 0.662 ln Tm -0.481 (ln Tm)2 and BMD (gHA/cm2) = 0.91 + 0.00711 ln Tm - 0.00846 (ln Tm)2 (in both cases p less than 0.001 and Tm expressed in months of menopause). After 20 years of menopause, 50 to 60% of normal women have vertebral BMC and BMD values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. We conclude that prevention of postmenopausal osteoporosis should be initiated as soon as possible after the onset of menopause and that bone density screening should be extended in elderly in order to detect and allow treatment of asymptomatic "densitometric" osteoporosis. [less ▲]

Influence of Specific Anti-Salmon Calcitonin Antibodies on Biological Effectiveness of Nasal Salmon Calcitonin in Paget's Disease of Bone

in Scandinavian Journal of Rheumatology (1990), 19(1), 83-6

Relationship between Whole Plasma Calcitonin Levels, Calcitonin Secretory Capacity, and Plasma Levels of Estrone in Healthy Women and Postmenopausal Osteoporotics

in Journal of Clinical Investigation (1989), 83(3), 1073-7

The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR ... [more ▼]

The exact role of calcitonin (CT) in the pathogenesis of postmenopausal osteoporosis remains unknown. Whole plasma calcitonin (iCT) basal levels, metabolic clearance rate (MCR), and production rate (PR) of CT were measured in 9 premenopausal and 16 postmenopausal women, including 11 osteoporotics (OP). Basal iCT levels were statistically lower in postmenopausal women than in the premenopausal group (P less than 0.01) and strongly correlated (r = 0.72; P less than 0.001) with estrone circulating levels (E1). MCR were similar in all groups. PR were similar in eugonadal women between 22 (mean +/- SD = 30.9 +/- 9.9 micrograms/d) and 37 yr (mean +/- SD = 25.5 +/- 11.1 micrograms/d) premenopausal women. In healthy postmenopausal women PR were reduced, but not significantly (mean +/- SD = 19.5 +/- 6.95 micrograms/d), whereas osteoporotic patients presented a highly significant reduction of CT PR (mean +/- SD = 9.8 +/- 4 micrograms/d) (P less than 0.01). Because there is a strong relationship between E1 and PR (r = 0.64; P less than 0.001), CT secretory capacity appears to be modulated by estrogen circulating levels. This modulation leads to a menopause-related decrease in iCT. In osteoporotics, an independent impairment of CT production drastically lowers PR and basal iCT levels. CT might be one of the determining factors in the pathogenesis of postmenopausal osteoporosis. [less ▲]

Prevention of Postmenopausal Bone Loss by Tiludronate

in Lancet (1989), 2(8678-8679, Dec 23-30), 1469-71

76 healthy women, who had been menopausal for less than 96 months and who had never received any form of treatment to prevent bone loss, were entered into a randomised double-blind study. For the first 6 ... [more ▼]

76 healthy women, who had been menopausal for less than 96 months and who had never received any form of treatment to prevent bone loss, were entered into a randomised double-blind study. For the first 6 months, half the patients received tiludronate 100 mg daily, while the others received placebo. During the second 6 months, all patients received placebo. Bone mineral density of the lumbar spine decreased significantly by 2.1% (SE 0.8%) in the placebo group and did not significantly change in the tiludronate group (+1.33 [0.8]%). The difference in response between the groups was significant, as were the differences between values for corrected urinary hydroxyproline and calcium. Treatment with tiludronate was not followed by increased secretion of parathyroid hormone. A 6 month course of oral tiludronate may counteract postmenopausal bone loss for at least a year by decreasing bone resorption. [less ▲]

Biological and Clinical Assessment of a New Bisphosphonate, (Chloro-4 Phenyl) Thiomethylene Bisphosphonate, in the Treatment of Paget's Disease of Bone

in BONE (1988), 9(6), 349-54

Several Biophosphonates have been used as therapeutic agents for Paget's bone disease. (Chloro-4 phenyl)thiomethylene-bisphosphonate (CIPsMBP) has recently been shown to have significant antiosteoclastic ... [more ▼]

Several Biophosphonates have been used as therapeutic agents for Paget's bone disease. (Chloro-4 phenyl)thiomethylene-bisphosphonate (CIPsMBP) has recently been shown to have significant antiosteoclastic activity while an affect of CIPsMBP on mineralization was only observed at high doses. We tested this drug for 6 months in 23 pagetic patients distributed in three groups. Gr 1 (n = 5) receiving 200 mg/day showed a decrease of serum alkaline phosphatase (SAP) to 42 +/- 4% (p less than 0.01) of initial value (100%) while hydroxyprolinuria/creatinuria ratio (OH/Cr) dropped to 69 +/- 8% of baseline. In 4 patients receiving 400 mg/day, SAP improved to 48 +/- 9% of initial value (p less than 0.01) and OH/Cr to 40 +/- 3% (p less than 0.01). In the last group (n = 14) receiving 200 mg/day for 3 months, and 400 mg/day thereafter up to the 6th month SAP decreased to 53 +/- 4% and OH/Cr to 62 +/- 6% of initial value (p less than 0.01). Clinical improvement was significant from the first month of treatment. No resistance (mean decrease of SAP lower than 30%) was recorded and no radiological or clinical evidence of mineralization defect appeared. The clinical and biological tolerance was excellent throughout the study. [less ▲]

1-Year Controlled Randomised Trial of Prevention of Early Postmenopausal Bone Loss by Intranasal Calcitonin

in Lancet (1987), 2(8574), 1481-3

79 women who had been menopausal for less than 36 months and who had not received any form of treatment to prevent bone loss were randomly assigned to a 12-month regimen of calcium 500 mg/day or calcium ... [more ▼]

79 women who had been menopausal for less than 36 months and who had not received any form of treatment to prevent bone loss were randomly assigned to a 12-month regimen of calcium 500 mg/day or calcium 500 mg plus intranasal salmon calcitonin 50 IU/day for 5 days per week. After 12 months of treatment bone mineral density had decreased in the calcium-only group by a mean of 3.16 (SEM 0.6)% (p less than 0.01) but had increased in the calcium plus calcitonin group by 1.38 (0.8)% (NS). The difference in response between the two treatment groups was also highly significant (p less than 0.01), as was the difference between values for hydroxyprolinuria/creatininuria (p less than 0.01). Endogenous calcitonin levels rose significantly in the calcium group but remained unchanged in calcitonin-treated patients. Treatment by calcitonin and calcium was not followed by increased secretion of parathyroid hormone. The findings suggest that intranasal calcitonin can counteract early postmenopausal bone loss. [less ▲]