Osteoporosis and exercise in women.
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Bone Density↗
Biomedical subjects
R Marcus
Publications and source records attributed to R Marcus.
The pre-ulcerative phase of carrageenan-induced colonic ulceration in the guinea-pig.
The pre-ulcerative phase of carrageenan-induced colonic ulceration was investigated in guinea-pigs supplied 3% degraded carrageenan as an aqueous solution as drinking fluid for 2 or 3 days during which no ulceration of the bowel was observed with the naked eye or dissecting microscope. Mucosal microscopic changes, from caecum to rectum, were multifocal and included cellular infiltrates, dilatation of glands, crypt abscesses, micro-ulcers and sulphated polysaccharide in the lamina propria. Sulphated polysaccharide was also demonstrated histologically for the first time within the surface epithelium and showed ultrastructural features similar to carrageenan. The results indicate that colonic epithelium in the guinea-pig is capable of macromolecular absorption. Carrageenan, a highly active polyanionic electrolyte, within the surface epithelial cells is most likely a primary factor in the breakdown of mucosal integrity. Macromolecular absorption causing enteropathy of the large bowel is a new pathophysiological concept which may have implications in man, particularly in the pathology of large bowel disease.
Animals↗
Chronic atypical seizure disorder and cataracts due to delayed diagnosis of pseudohypoparathyroidism.
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Adult↗
Multiple primary cutaneous plasmacytomas.
BACKGROUND: Cutaneous plasmacytoma is an uncommon tumor and is mostly seen in the context of end-stage multiple myeloma. Only 20 cases of primary cutaneous plasmacytoma have been documented. A significant proportion of these patients went on to develop systemic disease with a poor prognosis. In a number of patients, however, the abnormal clone of plasma cells may arise in the skin and never progress to multiple myeloma involving the bone marrow. OBSERVATIONS: We describe a patient who developed multiple primary cutaneous plasmacytomas after a possible insect bite reaction. The monoclonality of the tumor cells is demonstrated using immunohistochemical techniques. He has been treated vigorously with chemotherapy and local radiotherapy and remains well 3 years after diagnosis. Bone marrow has been harvested for use as an autologous bone marrow transplant in the event of systemic relapse. CONCLUSIONS: Unlike previous reports of this rare entity, this case documents the monoclonality of tissue plasma cells with immunohistochemical techniques. As cutaneous plasmacytomas have been reported with an early significant mortality, unlike extramedullary plasmacytomas elsewhere, we have advocated combination chemotherapy and cryopreservation of uninvolved bone marrow for future autologous bone marrow transplantation should systemic myelomatosis develop in the patient.
Adult↗
Growth hormone therapy in hypophosphatemic rickets.
The effects of growth hormone therapy on the biochemical measures of bone metabolism were studied in 11 children aged 3.5 to 17 years who had familial hypophosphatemic rickets; five were male. Subjects were maintained on a regimen of stable doses of conventional therapy (calcitriol and phosphate). Subjects were studied at baseline receiving conventional therapy and during three sequential treatment periods: no therapy (4 weeks), growth hormone only (0.05 mg/kg per day for 4 weeks), and conventional therapy plus growth hormone (2 weeks). The nine youngest subjects were continued on a regimen of triple therapy for an additional 24 weeks. Serum phosphate averaged 0.93 +/- 0.13 mmol/L (mean +/- SD) at entry and decreased when the subjects were not receiving any therapy. During the 4 weeks of growth hormone only treatment, phosphate rose in all 11 subjects (0.70 +/- 0.08 mmol/L to 0.83 +/- 0.08 mmol/L). With triple therapy, phosphate remained higher than with no therapy. Calcitriol, osteocalcin, and parathyroid hormone increased as the subjects received growth hormone alone. Insulinlike growth factor I z scores rose significantly in response to growth hormone therapy alone. All nine subjects receiving 6 months of triple therapy increased their growth rate z scores. Exogenous growth hormone therapy may be useful in familial hypophosphatemic rickets.
Adolescent↗
Noninvasive assessment of ulnar bending stiffness in women.
The load-carrying capacity of cortical bone is closely related to its geometry and to its fundamental material properties, including mineral content (BMC). Together these determine the bending stiffness EI, where I is the cross-sectional moment of inertia and E is Young's modulus of elasticity. To assess the relationship of BMC and bone width (BW) to EI in healthy women, we used mechanical response tissue analysis (MRTA), a noninvasive method that involves analysis of tissue responses to ulnar vibration. A total of 48 healthy women were enrolled into an older (64 +/- 1y, n = 25) and a younger (25 +/- 0.6y, n = 23) group. BMC and BW of the dominant ulna were measured by single-photon absorptiometry (SPA). EI was determined by MRTA. BMC (0.75 +/- 0.02 versus 0.63 +/- 0.02 g/cm), BMC/BW (0.75 +/- 0.02 versus 0.63 +/- 0.02 g/cm2), and EI (27.7 +/- 1.3 versus 21.3 +/- 1.1 N.m2) were significantly greater (p less than 0.005) in the young subjects. BW did not change with age (1.00 +/- 0.01 versus 1.01 +/- 0.01 cm). In young women, simple correlations of BMC and BW with EI were both significant. By multiple regression analysis only BW independently predicted EI (EI = -0.35 + 39.1 x BMC, R2 = 0.52). In older women BMC and BW correlated with EI, but in multiple regression only BMC was significant (EI = -34.5 + 62.1 x BW; R2 = 0.45). When this analysis of older women included only those whose BMC values were within 2 SD of the young mean, BMC remained the only significant predictor of EI.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Effects of voluntary exercise on bone mineral content in rats.
We used a voluntary running model to explore the relationship between average daily running distance and bone mineral status of rats. A total of 60 male Sprague-Dawley rats were randomly assigned at 6 weeks of age to a sedentary control group (n = 22) or to a group with unlimited access to a running wheel (n = 38). The running distance of exercising rats was monitored daily, and steady-state running levels ranged from 3.2 to 18.1 km/day. At the end of the experimental period, femora and tibiae were dissected and bone mineral content (BMC, g/cm) and bone mineral density (BMD, g/cm2) were measured by single-photon absorptiometry. Cross-sectional morphometry was examined by taking a transverse section of the femoral middiaphysis. Hindlimb percentage fat was significantly higher in controls than in runners (20.0 +/- 1.2 versus 11.1 +/- 0.6, p less than 0.001), and soleus mass was greater in runners than in controls (371 +/- 8.1 versus 320 +/- 0.8 mg, p less than 0.001). Femoral and tibial lengths, weights, and volumes were significantly higher in runners than in controls (p less than 0.005). BMC and BMD were higher in runners than in controls at all sites apart from the distal femur. Cross-sectional areas at the femoral midshaft were greater in running rats than in sedentary controls (6.26 +/- 0.1 versus 5.45 +/- 0.3 mm2, p less than 0.02), as was the polar moment of inertia (15.6 +/- 0.6 versus 12.7 +/- 0.2 mm4, p less than 0.05). No positive correlation was found between distance run and BMC, BMD, cross-sectional area, or polar moment of inertia.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Estrogens and progestins in the management of primary hyperparathyroidism.
One of the common dilemmas in clinical endocrine practice is the management of patients with hyperparathyroidism (HPT) who either cannot or will not undertake definitive surgical treatment. Therapeutic decisions would be simplified by the availability of a nonsurgical approach to control biochemical abnormalities and forestall the consequences of this condition. In the short term, oral phosphorus salts can be safe and effective. For chronic therapy, only estrogens and progestins have been examined in sufficient detail to merit discussion. Estrogens normalize serum and urinary calcium in the majority of older women with HPT. Biochemical control is generally maintained for as long as patients continue treatment. The data support the view that estrogen inhibits the actions of PTH, particularly on bone, but does not reduce the abnormal PTH secretion. Androgenic progestins may also lower serum and urinary calcium in HPT, but current data suggest that normalization of serum calcium levels is more likely to occur with estrogen. Although reduction in urinary calcium excretion should prove effective in preventing nephrolithiasis, it is unclear whether hormone therapy provides protection against fracture. Whether or not hormone replacement is prescribed, nonsurgical management requires a highly committed patient who is willing to undergo extensive and prolonged follow-up.
Administration, Oral↗
Graft-versus-host disease in solid organ transplantation.
Graft-versus-host disease is well recognized in bone marrow transplantation, but has only recently been described in solid organ transplantation. Two such cases in liver graft recipients, proven by the demonstration of donor type HLA antigens in the peripheral blood and marrow on tissue typing, are described in this paper. The literature on this subject is reviewed and the treatment discussed. It is postulated that there is an order of risk of development of graft-versus-host disease depending on the amount of viable lymphoid tissue included with the transplanted organ as follows: small bowel greater than heart-lung greater than liver greater than kidney greater than heart. It seems likely that this condition has been substantially underdiagnosed in the past and that greater awareness of the possibility of graft-versus-host disease in solid organ recipients will lead to the recognition of further cases and allow appropriate treatment to be promptly instituted.
Adult↗
Rational approaches to osteoporosis therapy.
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Age Factors↗
Muscle hypertrophy response to resistance training in older women.
We conducted a 12-wk resistance training program in elderly women [mean age 69 +/- 1.0 (SE) yr] to determine whether increases in muscle strength are associated with changes in cross-sectional fiber area of the vastus lateralis muscle. Twenty-seven healthy women were randomly assigned to either a control or exercise group. The program was satisfactorily completed and adequate biopsy material obtained from 6 controls and 13 exercisers. After initial testing of baseline maximal strength, exercisers began a training regimen consisting of seven exercises that stressed primary muscle groups of the lower extremities. No active intervention was prescribed for the controls. Increases in muscle strength of the exercising subjects were significant compared with baseline values (28-115%) in all muscle groups. No significant strength changes were observed in the controls. Cross-sectional area of type II muscle fibers significantly increased in the exercisers (20.1 +/- 6.8%, P = 0.02) compared with baseline. In contrast, no significant change in type II fiber area was observed in the controls. No significant changes in type I fiber area were found in either group. We conclude that a program of resistance exercise can be safely carried out by elderly women, such a program significantly increases muscle strength, and such gains are due, at least in part, to muscle hypertrophy.
Aged↗
High-dose chemoradiotherapy supported by marrow infusions for advanced neuroblastoma: a Pediatric Oncology Group study.
We conducted a pilot protocol at seven Pediatric Oncology Group (POG) institutions to examine the feasibility, toxicity, and efficacy of using a common regimen of high-dose chemoradiotherapy (HD CT/RT) supported by autologous or allogeneic marrow infusions in children with metastatic neuroblastoma (NBL) in first or second remission. During a 57-month period, we accrued 101 patients. We report here results for the 81 who completed treatment at least 2 years ago. The HD CT/RT regimen consisted of melphalan 60 mg/m2/d for three doses, and total body irradiation (TBI) either 1.5 Gy (n = 27) or 2.0 Gy (n = 54) twice daily for six doses. Twenty-three patients also received irradiation consisting of 1.2 Gy twice daily for 10 doses to persisting disease sites. Seventy-four were given autologous and seven allogeneic marrow, 64 autologous marrows being purged immunomagnetically. Fifty-four children were in first complete (CR) or partial (PR) remission and 27 in second CR or PR. As of October 1, 1990, follow-up was from 32 to 72 months. Forty-seven of these 81 children relapsed, 10 died of complications, one of unknown cause, and 23 continue in remission, including 21 of the 54 treated in first remission, and 16 who completed treatment more than 3 years ago. The 2-year actuarial event-free survival (EFS) probabilities are first CR (CR1) 32% (SE 10%), first PR (PR1) 43% (SE 9%), second CR (CR2) 33% (SE 27%), and second PR (PR2) 5% (SE 5%). Probability of EFS correlated with remission number (first better than second, P less than .001), with interval from diagnosis to HD CT/RT (greater than 9 months better than less than 9 months, P = .055), and with TBI dose (12 Gy better than 9 Gy, P = .031). These encouraging results may partly reflect selection for this treatment of patients with NBL who have a slower disease pace.
Adolescent↗
Successful treatment of acute myeloid leukemia beyond first remission with autologous bone marrow transplantation using busulfan/cyclophosphamide and unpurged marrow: the British autograft group experience.
The results in 34 adult patients with acute myeloid leukemia (AML) who have undergone autologous bone marrow transplantation (ABMT) using busulfan and cyclophosphamide (Bu/Cy) in 12 United Kingdom (UK) centers have been analyzed. There were 19 females and 15 males; median age was 40 years (range, 21 to 62 years). Nine patients were in first relapse; 25 were in second remission. The median time of first remission for the whole group was 11.5 months (range, 1 to 56 months). All the patients in first relapse and six patients in second remission received first remission marrow. The leukemia-free survival (LFS) for the patients in first relapse was 33%, with a median follow-up of 20 months. The LFS for the patients in second remission was 48% with a median follow-up of 26 months. The length of second remission exceeds the length of first remission in 14 patients. Considerable toxicity with hemorrhagic cystitis (four patients; none fatal), venoocclusive disease (four patients; one fatal), pneumonitis (four patients; one fatal), intracranial hemorrhage (two patients; two fatal) has occurred. There have been four procedure-related deaths (12%). Hematologic recovery was satisfactory for neutrophils (median time to 0.5 x 10(9)/L, 22 days [range, 11 to 101 days]), but very slow for platelets (median time to 50 x 10(9)/L, 62 days [range, 15 to 1,080 days]). This study suggests that the use of Bu/Cy with ABMT for patients beyond first remission in AML compares favorably with chemotherapy, and although the procedure-related mortality is acceptable, it is associated with protracted platelet recovery.
Acute Disease↗
The prognostic significance of autologous bone marrow transplant in advanced neuroblastoma.
This report provides strong evidence for conducting a controlled randomized clinical trial of autologous bone marrow transplantation versus conventional chemotherapy in childhood neuroblastoma, which is disseminated beyond the intracavity nodes, and which is diagnosed in children older than 12 months of age. On the basis of two Pediatric Oncology Group (POG) studies, one a surgery plus conventional chemotherapy study (POG 8441) and the other an elective autologous transplant pilot protocol (POG 8340), there was no significant prognostic benefit of switching in remission from the surgery plus chemotherapy protocol to the transplant protocol (P = .91) or of switching in remission from the surgery plus chemotherapy protocol to any transplant (P = .75). The analysis is based on 116 patients achieving a complete or partial remission, 32 of whom received transplants on the pilot protocol, and 17 of whom received transplants outside the pilot protocol. While potential selection bias precludes cause-effect conclusions, these data strongly suggest that a large randomized trial of autologous bone marrow transplantation should be conducted before accepting this form of therapy as standard.
Adolescent↗
Intensive chemotherapy and low-dose radiotherapy for the treatment of advanced-stage Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.
Sixty-two patients with advanced-stage Hodgkin's disease and a median age of 12 years (range, 3 to 22 years) were treated with four cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with four cycles of doxorubicin, vinblastine, bleomycin, and dacarbazine (ABVD) followed by low-dose radiotherapy (RT). We determined the feasibility, immediate safety, and rapidity of response of patients to this regimen, as well as the relationship between prognostic factors and the rate of complete remission (CR), event-free survival (EFS), and overall survival. Therapy was well tolerated, and the major toxicity was hematopoietic. At the end of chemotherapy, 54 of 62 patients (87%) were in CR by clinical restaging, with a biopsy of residual disease where necessary. The actuarial 3-year EFS is 77% (SE, 11%), with a median follow-up of 35 months, and the survival is 91% (SE, 7%). With respect to EFS, female patients and those with stage II or III disease fared statistically better than males and patients with stage IV disease, respectively. Six patients have died: three of progressive Hodgkin's disease, one of secondary acute myelocytic leukemia (AML), one of secondary non-Hodgkin's lymphoma (NHL), and one of overwhelming bacterial sepsis. The Pediatric Oncology Group (POG) is currently engaged in a randomized study of these eight cycles of chemotherapy with and without RT to assess the role of RT in achieving comparable results.
Adolescent↗
Recovery from osteopenia in adolescent girls with anorexia nervosa.
Osteopenia is a frequent complication of anorexia nervosa (AN). To determine whether the deficit in bone mineral changes during the course of this illness, we studied 15 adolescent patients prospectively for 12-16 months using dual photon absorptiometry of the spine and whole body. At follow-up, mean weight, height, and body mass index (BMI) had increased significantly, although 6 girls had further weight loss or minimal gain (less than 1.2 kg). Spontaneous menses occurred in 2 girls, and 3 others were given estrogen replacement. Bone mineral density of the lumbar spine did not change significantly (mean +/- SD, 0.836 +/- 0.137 vs. 0.855 +/- 0.096 g/cm2), while whole body bone mineral density increased (0.710 +/- 0.118 vs. 0.773 +/- 0.105; P less than 0.05). Despite gains in bone mineral, 8 patients had osteopenia of the spine and/or whole body. Changes in weight, height, and BMI were significant predictors of change in bone mineral density. Increased bone mass occurred with weight gain before return of menses; conversely, weight loss was associated with further decreases in bone density. In 1 patient who failed to gain weight, estrogen therapy resulted in increased spinal, but not whole body, bone mineral. We also studied a second group of 9 women who had recovered from AN during adolescence. All 9 had normal whole body bone mineral for age, but 3 had osteopenia of the lumbar spine. We conclude that osteopenia in adolescents with AN reflects bone loss, perhaps combined with decreased bone accretion. Weight rehabilitation results in increased bone mineral before the return of menses. Estrogen may have an independent effect on bone mass. The persistence of osteopenia after recovery indicates that deficits in bone mineral acquired during adolescence may not be completely reversible.
Adolescent↗
Effects of aluminum hydroxide on the parathyroid-vitamin D axis of postmenopausal women.
In previous studies we proposed that estrogen increases circulating calcitriol in postmenopausal women by reducing plasma phosphorus concentrations. For this model to be plausible, a reduction in plasma phosphorus must be itself be sufficient to increase circulating calcitriol in elderly women. To assess this question we studied the effects of Al(OH)3 on daylong circulating levels of phosphorus, calcium, PTH, and calcitriol in 14 postmenopausal women. Subjects were studied on two 7-day periods of dietary control, in which calculated intakes for phosphorus, calcium, and sodium were 950, 800, and 3000 mg/day, respectively. During one randomly assigned period, subjects were given Al(OH)3 with each meal. Al(OH)3 significantly lowered daylong plasma phosphorus concentrations by 17% (0.95 +/- 0.02 mmol/L vs. 1.15 +/- 0.02, P less than 0.0005) (2.94 +/- 0.06 mg/dL vs. 3.57 +/- 0.07), and this was associated with a 38% rise in circulating calcitriol from 61.8 +/- 10.3 pmol/L to 85.2 +/- 10.1 pmol/L (25.7 +/- 4.3 pg/ml to 35.5 +/- 4.2 pg/ml) (P less than 0.0001). The rise in calcitriol correlated significantly with the reduction in phosphorus (r = 0.51, P = 0.03). Al(OH)3 did not significantly alter average daily circulating total calcium (2.32 +/- 0.008 vs. 2.32 +/- 0.005 mmol/L) (9.31 +/- 0.03 vs. 9.29 +/- 0.02 mg/dL), ionized calcium (1.19 +/- 0.003 vs. 1.19 +/- .004 mmol/L), or intact PTH (24.6 +/- 0.6 vs. 24.2 +/- 0.8 ng/L). Moreover, neither the renal phosphorus reabsorption maximum (TmP/GFR), baseline excretion of cAMP, nor the phosphaturic, cAMP, or calcitriol responses to infused hPTH(1-34) were altered by Al(OH)3. We conclude that Al(OH)3 treatment of older women lowers plasma phosphorus concentrations by restricting intestinal phosphorus absorption, and that older women retain the capacity to increase calcitriol levels in response to phosphorus restriction.
Aged↗
Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls.
We studied the acquisition of bone mineral in 45 healthy prepubertal and pubertal girls and related changes in bone mass to age, body mass, pubertal status, calcium intake, and exercise. A subgroup of 12 girls was followed longitudinally. Bone mineral content (BMC) of the lumbar spine, whole body, and femoral neck was measured by dual energy x-ray absorptiometry and that at the midradius by single photon absorptiometry. For comparison, spine and whole body mineral contents were also measured by dual photon absorptiometry. Bone mass was expressed in conventional terms of BMC and area density (BMD). However, we show that BMD fails to account for differences in bone thickness. Since bone size increases during adolescence, we present a new expression, bone mineral apparent density (BMAD), which is BMC normalized to a derived bone reference volume. This term minimizes the effect of bone geometry and allows comparisons of mineral status among bones of similar shape but different size. BMC increased with age at all sites. These increases were most rapid in the early teens and plateaued after 16 yr of age. When bone mineral values at all sites were regressed against age, height, weight, or pubertal stage, consistent relationships emerged, in which BMC was most strongly correlated, BMD was correlated to an intermediate degree, and BMAD correlated only modestly or without significance. Dietary calcium and exercise level did not correlate significantly with bone mass. From these relationships, we attribute 50% of the pubertal increase in spine mineral and 99% of the change in whole body mineral to bone expansion rather than to an increase in bone mineral per unit volume. In multiple regressions, pubertal stage most consistently predicted mineral status. This study emphasizes the importance of pubertal development and body size as determinants of bone acquisition in girls. BMAD may prove to be particularly useful in studies of bone acquisition during periods of rapid skeletal growth.
Absorptiometry, Photon↗