Grethe Finn Jensen

Thiazide for the postponement of postmenopausal bone loss

The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.

Seasonal variations in indices of bone formation precede appropriate bone mineral changes in normal men

In 10 normal males aged 23-50 years measurements of serum alkaline phosphatase (s-AP) and the 24-h whole body retention of 99mTc-diphosphonate (WBR), as indices of bone formation, and the fasting urinary hydroxyproline:creatinine ratio (OHPr:Cr), as an index of bone resorption, were performed monthly from January 1983 to May 1984. Bone mineral content of the distal forearm (BMC) was measured in the middle of each quarter. From January to May BMC exhibited a reproducible, significant average increase of 2.5%, returning to baseline level between May and August. During the first quarter of both 1983 and 1984 a significant increase in s-AP and WBR was seen. Subsequently, during the second quarter of 1983, these variables fell below the mean of the year. Confirming their interrelationship, the deviations of s-AP and WBR were positively correlated throughout the study period (r = 0.51, P less than 0.05). Since the urinary OHPr:Cr ratio remained constant, the reported seasonal changes in bone mass of normal, adult males appear to result from primary changes in bone formation.

Factors in response to treatment of early postmenopausal bone loss

SummaryBone mineral content (BMC) was measured by125I photon absorptiometry every 3 months in 264 normal females (45–54 years) over a 2-year period together with serum samples for calcium, phosphate, magnesium, creatinine, alkaline phosphatases, potassium, and protein. A 48-h urinary calcium and creatinine measurement was obtained. The subjects were divided into 7 treatment groups and 3 placebo groups. Five of the treatments (thiazide, vitamin D3, fluoride + vitamin D3, fluoride, and 1αD3) were ineffective at the doses used; the annual loss of compact bone was 1.5–2.2% (-X=1.8%), similar to the loss seen with placebos. Estrogen and estrogen + thiazide, in contrast, produced a 1.34% annual increase of BMC.The subjects were divided into groups with low, medium, and high initial BMC. Also, individual regressions for bone change were calculated and the subjects were divided into groups of responders, maintainers, and losers (annual change of >0%, 0 to −1%, and >−1%, respectively).The initial BMC status did not consistently affect bone or biochemical responses to the therapeutic agents. Estrogen was effective even in subjects with high BMC, whereas the other agents did not inhibit bone loss even in subjects with low initial BMC. Virtually all subjects responded to estrogen positively; in contrast we could not identify a subset of “responders” with any of the other treatments. Time since menopause appeared to influence the bone changes, although it was not a significant effect given the sample size. Bone loss in groups not treated with estrogens was 2%/year at 20 months after menopause with a decline to 1.3%/year at 45 months post-menopause. There was no apparent decline in the bone response to estrogen during the first 4 years after menopause, and in fact bone response tended to increase with time.

Low-Power Laser Therapy in Rheumatoid Arthritis

Thirty-five patients suffering from rheumatoid arthritis were allocated at random to treatment with either a low-power laser (3.58 J cm−2, continuous wave 820 nm) or a placebo in a 4-week, double-blind study. Eight finger joints (2nd–5th metacarpo- and proximal interphalangeal joints) of the most affected hand were treated. In the laser group the grip strength and finger flexibility improved, the swelling of the joints declined, the morning stiffness and pain decreased. The sedimentation rate and the number of leukocytes showed a fall with a significant trend. In the placebo group there were no changes in these parameters except for the registration of pain, where a significant, less than with the laser, effect was observed. Thus, low-power laser therapy, at the chosen wavelength and energy dose, appears to be effective against the classical complaints from rheumatoid arthritis.

Urinary 99m-Tc-diphosphonate excretion as a simple method to quantify bone metabolism

Twenty-four-hour whole-body retention (WBR) of 99m-Tc-methylene-diphosphonate (an index of bone turnover) was determined by whole-body counting (WBRs) and complementarily by urine counting (WBRu) in nineteen subjects with normal to highly increased bone turnover. WBRs and WBRu correlated well (r = 0.94, P less than 0.001), and gave almost the same results. Both WBRs correlated equally well with serum alkaline phosphatase and urine hydroxyproline/creatinine (r = 0.82-0.93). Coefficient of variation in WBRu was 7.0%, determined by duplicate measurements in sixteen normals. The injected dose of diphosphonate did not influence WBRu. However, since almost 50% of the diphosphonate excreted in urine appeared during the first few hours after the i.v. injection, the method of WBRu requires careful urine collection. Thus, the simple WBRu determination provides the same information on bone metabolism as does the more cumbersome and expensive WBRs technique.

Bone mass as referent for urinary hydroxyproline excretion: age and sex-related changes in 125 normals and in primary hyperparathyroidism

SummaryFasting urinary hydroxyproline:creatinine ratio (OHPr:Cr) and bone mineral content of the forearm (BMC) were measured in 125 normals, 67 females and 58 males, aged 20–79 years, and in 15 patients with primary hyperparathyroidism. In normals, both variables were significantly correlated to age and sex. The interrelation of OHPr:Cr and BMC was studied in subgroups of normals who were supposedly in metabolic balance, that is, females aged 20–39 years (n=24) and males aged 20–49 years (n=29). In both sexes OHPr:Cr and BMC were positively correlated: r=0.60 and 0.58, respectively (P<0.001). On this basis, BMC correction of all OHPr:Cr values was undertaken now revealing a stable increased level of bone resorption per unit of bone mass in post-menopausal females. In males OHPr:Cr per unit of BMC remained unaltered throughout life. In primary hyperparathyroidism, in which increased bone resorption is inherent, the discriminatory power of OHPr:Cr was significantly improved when calculated per unit of BMC (P<0.001). These observations suggest that estimation of bone resorption by use of OHPr:Cr requires adjustment for differences in bone mass.

Fracture Frequency and Bone Preservation in Postmenopausal Women Treated with Estrogen

Two hundred eighty-five normal 70-year-old Danish women were divided according to postmenopausal use of gonadal hormones into 3 groups: 1 virtually untreated (3 months or less, N = 231), 1 treated over a short term (4 months to 6 years, TV = 36), and 1 treated over a long term (6 years or more, N = 18). The 3 groups had been treated for a median of 0, 6, and 70%, respectively, of their postmenopausal years. The degree of bone loss varied inversely with the duration of postmenopausal hormone treatment. Bone mineral content was 11.87c higher in the long-term treated group than in the untreated group (P < .05). Likewise, the metacarpal bone mass was 8.5% greater (P < .01). The number of women with postmenopausal fractures was 13% lower in the long-term treated group than in the untreated group (difference not significant). Data from this retrospective study present evidence that estrogen protects bones in elderly women.

Measurements of whole body retention of diphosphonate and other indices of bone metabolism in 125 normals: dependency on age, sex and glomerular filtration.

Measurements of 24-h whole body retention of 99m-Tc-MDP (WBR) has been performed in 125 normal volunteers, together with determinations of serum alkaline phosphatase, urinary hydroxyproline excretion and creatinine clearance. WBR decreased slightly from the 3rd to the 4th decade, after which it increased gradually in the older age-groups. Serum alkaline phosphatase followed an identical pattern, while the urinary hydroxyproline excretion demonstrated a marked but temporary rise in the post-menopausal age-groups. Finally, the creatinine clearance decreased gradually in the older age groups. Analysis of variance demonstrated that WBR varied independently with serum alkaline phosphatase and creatinine clearance, while no relationship between WBR and the hydroxyproline excretion was found. It seems likely that the increasing retention of diphosphonate in elderly persons reflects rising osteoblastic activity as well as decreasing glomerular filtration.