D Denis

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

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.

PREVENTION OF POSTMENOPAUSAL BONE LOSS BY TILUDRONATE

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.

Relationship between whole plasma calcitonin levels, calcitonin secretory capacity, and plasma levels of estrone in healthy women and postmenopausal osteoporotics.

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.

Biological and clinical assessment of a new bisphosphonate, (chloro-4 phenyl)thiomethylene bisphosphonate, in the treatment of Paget's disease of bone

Several Biophosphonates have been used as therapeutic agents for Pagets 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.

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

(1990). Influence of Specific Anti-Salmon Calcitonin Antibodies on Biological Effectiveness of Nasal Salmon Calcitonin in Pagets Disease of Bone. Scandinavian Journal of Rheumatology: Vol. 19, No. 1, pp. 83-86.

Dual photon absorptiometry of lumbar spine in West European (Belgian) postmenopausal females: normal range and fracture threshold

SummaryBone 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)=41.6+0.662 ln Tm −0.481 (ln Tm)2 and BMD (gHA/cm2)=0.91+0.00711 in Tm −0.00846 (ln Tm)2 (in both cases p<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.

Is there any place for salmon calcitonin in prevention of postmenopausal bone loss

Introduction Postmenopausal bone loss and subsequent osteoporosis (OP) are consequences of a change in bone turnover leading to an imbalance between resorption and formation1. One of the most effective ways of preventing postmenopausal bone loss, or at least of slowing its rate, is to use estrogen replacement therapy (ERT), either alone or in combination with a progestogen2,3. However, the dose of estrogen required to produce a net gain of bone is much higher than that required to control other postmenopausal symptoms4, hence the risk of adverse effects is greater, which makes ERT unsuitable for many postmenopausal women. For a large subset of postmenopausal women there is thus an urgent need for an alternative to ERT in order to prevent excessive bone loss.

Influence of the nature of calcium salts on serum calcium, phosphorus, calcitonin, growth hormone, and somatomedin C.

SummaryTwenty healthy males were randomly divided into three groups. Each subject received either 405 mg elemental calcium (Ca) as a salt linked to an amino acid precursor, 405 mg CaC12 or 1000 mg Ca as Ca gluconolactate and carbonate. In all three cases, Ca intake led to an increase of serum Ca and TCT production and a decrease of PTH liberation. However, when Ca is linked to the amino acid precursor, an elective stimulation of growth hormone (GH) and somatomedin C (SmC) occurs. Due to the nature of its amino acid precursor, this salt seems to stimulate GH and SmC liberation through hypophysis. This could be a major pathway in decoupling of the sequence resorption-formation and therapy of metabolic bone diseases.