H. Rico

TOTAL AND REGIONAL BONE MINERAL CONTENT AND FRACTURE RATE IN POSTMENOPAUSAL OSTEOPOROSIS TREATED WITH SALMON CALCITONIN : A PROSPECTIVE STUDY

Seventy-two postmenopausal osteoporotic women having more than one nontraumatic vertebral crush fracture were studied. Thirty-six of them, aged 68.8±1.2 years (18±4 YSM-years since menopause), were treated with 100 IU/day of salmon calcitonin i.m. plus 500 mg of elemental calcium for 10 days each month. The remaining 36 patients, aged 69.6±1.4 years (19±3 YSM), were given only 500 mg of elemental calcium for 10 days each month. All patients underwent clinical and analytical evaluation every 3 months. Radiological evaluation, assessment of vertebral deformities, and metacarpal radiogrammetry were done every 6 months. Densitometric measurements of total and regional bone mass were made every 12 months. At 24 months, the calcitonin group showed a 60% reduction in the number of new fractures and the group receiving only calcium had a 45% increase (P<0.001). The incidence of vertebral fractures was 0.07 per patient-year in the group treated with calcitonin and 0.45 per patient-year in the group treated with calcium (P<0.001). At 2 years, the calcitonin group showed a 12% increase in cortical bone mass on metacarpal radiogrammetry, a 16% increase in the axial skeleton on trunk densitometry, a 3.5% increase in total body bone mineral content, a 30.7% increase in pelvic bone mineral content, and a 6.2% increase in arm bone mineral content (all P<0.001). In the group treated with calcium alone there was a loss of bone mass in every region. These findings suggest that salmon calcitonin is effective in the treatment of osteoporosis and show that it acts on cortical and trabecular bone.

Effect of Silicon Supplement on Osteopenia Induced by Ovariectomy in Rats

Abstract. The effect of silicon (Si) supplement on preventing bone mass loss induced by ovariectomy (OVX) in rats was investigated. Three groups of 15, 100-day-old female Wistar rats each, with a mean initial weight of ∼260 g per animal, were selected for the present study. One of the experimental group consisting of 15 OVX rats was fed a diet supplemented with 500 mg of Si per kg of feed (Si + OVX). The other two groups consisting of 15 OVX and 15 sham-OVX rats did not receive these supplements. Morphometric (weight and length) and densitometric studies with dual-energy X-ray absorptiometry were performed on the whole femur and 5th lumbar vertebra of each animal 30 days after the experiment. The Si + OVX rats did not show a loss of bone mass induced by OVX at axial level (5th lumbar vertebra) or periphery (femur). Nonetheless, a significant increase (ANOVA with Bonferroni/Dunn post hocs test) of longitudinal development of the femur (P < 0.0001) was patent. These results, obtained through the measurements of axial and peripheral bones, warrant closer scrutiny in connection with the Si inhibitory effect on bone mass loss as well as the stimulatory effect on bone formation. Both actions, namely, inhibition of resorption and stimulation of formation, infer that Si may have a potential therapeutic application in the treatment of involutive osteoporosis.

Effect of Lead on Bone Development and Bone Mass: A Morphometric, Densitometric, and Histomorphometric Study in Growing Rats

Abstract. The effect of exposure to lead on the longitudinal development of bone and on bone mass was studied in rats. A group of 35, 50-day-old female Wistar rats was divided into a control group of 15 rats and an experimental group of 20 rats fed a diet supplemented with 17 mg of lead acetate per kg feed for 50 days. Total body bone densitometry (TBBMC) was performed the day before ending the 50-day experiment. On day 50, all rats were killed and their right femur and 5th lumbar vertebra were dissected. The bones were cleaned of soft tissue and femoral length and vertebral length were measured with a caliper and all bones were weighed on a precision scale. Final body weight (P < 0.05), TBBMC (P < 0.005), and femur weight (P < 0.005) were significantly lower in the control group. Femur length did not differ between groups, but the length of the 5th lumbar vertebra was greater in the control group (P < 0.05). Histomorphometry of the femur showed that Cn-BV/TV, Tb-N, Tb-Th were lower (P < 0.05 in all) and Tb-Sp was higher (P < 0.05) in the group given the lead-supplemented diet. These findings suggested lead-induced inhibition of axial bone development and a histomorphometric decrease in bone mass, produced mainly by enhanced resorption, and a densitometric increase in bone mass, produced by lead accumulation in bone.

Cortical versus trabecular bone mass: Influence of activity on both bone components

Motivated by the controversy in the literature concerning the influence of activity on bone mass and on its cortical and trabecular components, a study was made using computed peripheral tomography (Stratec XCT 900) of the total, cortical, and trabecular bone mass of the dominant and nondominant upper extremities of 50 apparently normal subjects (average age 26±6 years). No differences were observed in the trabecular bone compartment, but the cortical compartment was greater (P<0.001) in the dominant extremity. There was also a significantly greater total bone mass in the dominant extremity which we attributed to greater cortical mass (P<0.025) given the highly significant correlation (r2=0.904, P=0.0001) between total and cortical bone mass and the less significant correlation between total and trabecular bone mass (r2=0.479, P=0.0001).

Age-related differences in total and regional bone mass: A cross-sectional study with DXA in 429 normal women

Total body bone mineral content (TBBMC), total body bone mineral density (TBBMD) and regional bone mineral content (BMC) and density (BMD) were assessed by dual-energy X-ray absorptiometry (DXA) in 429 normal women aged 15–83 years, of whom 242 were premenopausal and 187 postmenopausal. The population was divided into 5-year age groups. In the premenopausal women no changes in TBBMC, TBBMD or regional BMC and BMD were observed with age, and TBBMC and TBBMD values correlated well with body weight (p<0.001). Postmenopausal women showed an overall reduction in bone mass (p<0.001), more marked at the axial level than peripherally (1.6% vs. 0.8%/year). The values of TBBMC and TBBMD correlated well with chronological age, time since the onset of menopause and body weight (p<0.001). In these women age did not correlate with body weight, which suggests that postmenopausal bone mass loss depends more on chronological age and time since the onset of menopause than on other variables. The stability observed in bone mass values from ages 15–19 to menopause highlights the importance of stimulating the acquisition of an appropriate peak bone mass in women before adolescence begins.

Effects on bone loss of manganese alone or with copper supplement in ovariectomized rats. A morphometric and densitomeric study.

OBJECTIVE The aim of this study was to examine the effect of manganese (Mn) alone and with the addition of copper (Cu) in the inhibition of osteopenia induced by ovariectomy (OVX) in rats. STUDY CONDITIONS: Four lots of 100-day-old female Wistar rats were divided into experimental groups of 15 each. One group received a diet supplemented with 40 mg/kg of Mn per kilogram of feed (OVX+Mn). The second group received the same diet as the first, but with an additional 15 mg/kg of copper (OVX+Mn+Cu). The third group of 15 OVX and the fourth group of 15 Sham-OVX received no supplements. At the conclusion of the 30-day experiment, the rats were slaughtered and their femurs and fifth lumbar vertebrae were dissected. Femoral and vertebral length were measured with caliper and bones were weighed on a precision balance. The bone mineral content (BMC) and bone density (BMD) of the femur (F-BMC, mg and F-BMD, mg/cm(2)) and the fifth lumbar vertebra (V-BMC, mg and V-BMD, mg/cm(2)) were measured separately with dual energy X-ray absorptiometry. RESULTS The F-BMD, mg/cm(2) was lower in the OVX than in the Sham-OVX group (P<0.0001) and in the other two groups receiving mineral supplements (P<0.005 in both). F-BMC, mg was significantly lower in the OVX group than in the other three (P<0.0001 in all cases). Calculations for V-BMC, mg and V-BMD, mg/cm(2) are similar to findings in the femur. CONCLUSIONS These data show that a Mn supplement is an effective inhibitor of loss of bone mass after OVX, both on the axial and the peripheral levels, although this effect is not enhanced with the addition of Cu.

Effects of zinc supplementation on vertebral and femoral bone mass in rats on strenuous treadmill training exercise

The hypothesis that a zinc (Zn) deficit may cause osteopenia in athletes is well founded. In rats exposed to strenous exercise, we evaluated the effect of a zinc supplement on femoral and vertebral bone mass determined by dual‐energy X‐ray absorptiometry. Four lots of 93‐day‐old female Wistar rats were studied. A control group of 30 rats were not manipulated (Zn– Ex– group). The experimental group of 40 rats was fed a diet supplemented with an additional 20% of Zn/kg of feed; this group was divided into two groups of 20 rats each, one that did not exercise (Zn+ Ex–) and one that did (Zn+ Ex+). A group of 15 rats exercised but did not receive a zinc supplement (Zn– Ex+ group). Training consisted of treadmill running for 5 out of 7 days over an 11‐week period. Initial speed, running time, and treadmill speed were increased gradually. Analysis of variance with the Bonferroni/Dunn test showed that the length, weight, bone mineral content (BMC), and bone mineral density (BMD) of the femur were less in the Zn– Ex+ group than in the others (p < 0.008), and the weight, BMC, and BMD of the fifth lumbar vertebra also were lower in the Zn– Ex+ group than in the others (p < 0.008). These findings confirm the adverse effects of strenuous exercise (treadmill running) on bone tissue in rats and the effectiveness of zinc supplementation in preventing it.

Total and regional bone mineral content in women treated with GnRH agonists

SummaryChanges in bone mineral content induced by GnRH agonists were investigated by measuring total body bone mineral content (TBBM) and regional bone mineral content (BMC) (arms, legs, trunk, pelvis) and densities with dual energy X-ray absorptiometry in 25 premenopausal women before and after a 6-month treatment with gonadotropin-releasing hormone (GnRH) agonists. Biological markers of bone remodeling, estrogens, luteinizing hormone, and follicle-stimulating hormone were also measured. Weight and body mass index increased significantly after treatment (P<0.05), and TBBM, corrected for weight (TBBM/W), decreased (P<0.001). The changes in BMC that we observed ranged from +2.5% to -6.9%. The greatest decrease in regional BMC occurred in the trunk (4.4%, P<0.001), with TBBM decreasing by 2.1% (P<0.001). No significant changes were observed in the limbs. Tartrate-resistant acid phosphatase (TRAP) increased significantly after treatment (P<0.001) and a significant negative correlation between TRAP and TBBM (P<0.001) and between TRAP and estradiol (P<0.001) were observed before treatment. The lack of changes observed in the BMC of the limbs indicate that GnRH agonists cause a preferential loss of BMC in trunk osseous structures, a situation similar to that of the first years of menopause.

The Therapy of Osteoporosis and the Importance of Cortical Bone

It is generally accepted that it is particularly important to increase trabecular bone mass in the treatment of osteoporosis. The cortical bone compartment is either overlooked entirely or its importance is underestimated, although cortical bone represents 80% of bone mass. This is an unfortunate oversight which has lead to the dissemination of an erroneous concept. There are many differences between trabecular bone and cortical bone that suggest that these bone compartments are distinctive structures with characteristic behavior and responses. Ninomiya et al. [1] published ‘‘Heterogeneity of Human Bone,’’ in 1990, a paper that summarized the differences between the trabecular and cortical bone compartments. They reported that cortical bone contains much more osteocalcin and less osteonectin than trabecular bone; therefore, cortical and trabecular bone may be subject to different regulatory mechanisms. Other relevant observations indicate important differences between the trabecular and cortical compartments. Eriksen et al. [2] reported that bone remodeling has a different duration in the cortical and trabecular bone compartments, which indicates fundamental differences in metabolism. Bone remodeling requires 200 days in trabecular bone, but only 120 days in cortical bone. This difference in metabolism was confirmed by our early study with peripheral quantitative computed tomodensitometric (pQCT) [3], a method that measures cortical and trabecular bone mass separately. In the early years of menopause, only trabecular bone mass showed a significant loss. Later, trabecular and cortical bone continued to behave differently, then, about 15 years after menopause and coinciding roughly with the presentation of vertebral osteoporosis, only the cortical compartment showed significant bone loss. Another important study showed that in normal individuals in whom trabecular and cortical bone mass were determined in the dominant and nondominant upper limb using pQCT, differences in cortical bone mass were found only in the dominant limb; the trabecular compartment was unaffected by the greater physical activity of this limb [4]. Other important observations underline the differences between trabecular and cortical bone. A few years ago Riggs et al. [5], in a study of fluoride in the treatment of osteoporosis, reported that fluoride was ineffective in cortical bone, which decreased in determinations made in the middle radius. Fluoride had anabolic effects only in trabecular bone, which increased in every site where it was determined. More bone fractures were observed in the group of women treated with fluoride than in the group treated with placebo, which obviously was related to the reduction in the cortical compartment rather than the quality of the fluoride-induced bone. Chappard et al. [6] reached similar conclusions after observing that cortical bone was resistant to the action of a biphosphonate and trabecular bone was more sensitive. Parathyroid hormone has been reported to have similar effects on bone [7]. Therefore, many conditions indicate that there are marked differences between the trabecular and cortical bone compartments. Likewise, and again in contrast with general opinion, cortical bone loss in postmenopausal and senile osteoporosis is greater than trabecular bone loss. In a pioneering study of this topic, Nottestrand et al. [8] found that the proportion of trabecular bone in vertebrae did not differ between osteoporotic women and normal women, which indicated that the cortical bone compartment had experienced most of the bone loss. Our findings in hip fractures considered to be osteoporotic [9] were similar: cortical osteoporosis was present in 95% of cases regardless of whether the hip fracture was trochanteric or cervical, but trabecular osteoporosis was present in only 78%. Uitewaal et al. [10] reported comparable results in vertebral and senile osteoporosis, in which they observed a major and significant loss of cortical bone thickness evaluated by histomorphometry. Compared with reference values for cortical thickness of 872 ± 418 m in persons over 50 (senile osteoporosis), patients with vertebral fractures had values of 604 ± 228 m (P < 0.05), patients with cervical hip fractures had values of 624 ± 225 m (P < 0.05), and patients with trochanteric fractures had values of 626 ± 315 m (P < 0.05). Kimmel et al. [11] and Foldes et al. [12] reported similar findings in histomorphometric studies. More recently, Steiniche [13] encountered a more marked and significant reduction in cortical bone width (P < 0.001) than in trabecular bone volume (P < 0.01) in women with postmenopausal osteoporosis compared with normal women. Using another technique, (99)mTc-MDP, Hardoff et al. [14] showed that bone turnover is significantly higher in the cortical bone of women with osteoporosis than in normal Correspondence to: H. Rico Calcif Tissue Int (1997) 61:431–432

CORTICAL BONE RESORPTION IN OSTEOPOROSIS

Abstract. A study was made of 110 women: 35 healthy premenopausal, 40 healthy postmenopausal, and 35 women diagnosed as having postmenopausal osteoporosis. The postmenopausal women had similar ages and years since menopause (YSM). In all of the women, total bone mass was evaluated by dual-energy X-ray absorptiometry and metacarpal morphometry was evaluated by radiogrammetry on the second metacarpal of the nondominant hand, performed by computed radiography. An external metacarpal diameter of ≥7.4 mm was required as proof of having developed an adequate peak bone mass. The endosteal diameter, which is indicative of bone resorption in both groups of postmenopausal women, obtained in the postmenopausal groups was subtracted from the endosteal diameter obtained in the premenopausal group and the resulting figure was divided by the years since menopause to calculate the rate of cortical bone resorption/year for each group. The endosteal diameters values differed in the three groups studied (P < 0.0001): 3.2 ± 0.7 mm in the healthy premenopausal women; 3.9 ± 0.6 mm in the healthy postmenopausal women; and 4.7 ± 0.5 mm in the osteoporotic postmenopausal women. The rate of cortical bone resorption was 0.068 ± 0.002 mm/YSM (years since menopause) in the osteoporotic postmenopausal women and 0.033 ± 0.003 mm/YSM in the healthy postmenopausal women (P < 0.0001). These figures reflect the importance of bone resorption, as opposed to deficient bone formation, as a cause of osteoporosis.