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S F Hodgson

Publications and source records attributed to S F Hodgson.

At least 37 records · Page 2Linked to original sources

Relationship between serum intact parathyroid hormone concentrations and bone remodeling in type I osteoporosis: evidence that skeletal sensitivity is increased.

To define the role of parathyroid gland function in the pathophysiology of bone loss in type I (postmenopausal) osteoporosis, we measured serum intact parathyroid hormone (PTH) concentration by immunoradiometric assay (IRMA) and by multisite immunochemiluminometric assay (ICMA) in 63 postmenopausal osteoporotic women (PMOp) with vertebral compression fractures and in 75 age-comparable postmenopausal normal women (PMNl). Also, tetracycline-based histomorphometric indices in cancellous bone were assessed in iliac biopsy samples from 61 PMOp and 28 PMNl women. Serum PTH concentrations by IRMA were similar in PMOp and PMNl (medians, 3.92 and 3.77 pmol/l; NS) but were significantly lower in PMOp by the more sensitive ICMA (medians, 2.82 and 3.14 pmol/l; P less than 0.01). By multiple linear regression analysis, serum PTH was directly related (P less than 0.001) to activation frequency, bone resorption rate, bone formation rate, and the calculated rate of bone loss. For each unit (pmol/l) increase in serum PTH by ICMA, activation frequency increased by 1.3%/year more (P = 0.01), bone resorption rate increased by 3.9%/year more (P = 0.003), and the rate of cancellous bone loss was 2.8% greater (P = 0.0003) in the PMOp women compared with the PMNl women. Concentrations of serum estradiol, but not serum estrone, had a weak opposing effect to PTH, especially for bone formation rate. These data suggest that in PMOp the bone has increased sensitivity to the biologic effects of PTH. This may represent one of the fundamental pathophysiologic defects in PMOp and, in the setting of estrogen deficiency, may explain, in part, their greater rate of bone loss.

Aged↗

Corticosteroid-induced osteoporosis.

Glucocorticoid-induced bone loss has been recognized for almost 50 years, yet it remains an important medical problem and a common cause of fracturing. Loss of skeletal mass may occur early in the course of glucocorticoid therapy and appears to be related to the cumulative dose of steroid, as well as to the usual risk factors for osteoporosis. The pathophysiology of this disorder is poorly understood, but available information suggests that glucocorticoids exert direct and indirect actions on bone and calcium homeostasis that may contribute to osteopenia. Direct effects appear to occur soon after the initiation of glucocorticoid therapy and include (1) suppression of intestinal calcium absorption, (2) decreased renal tubular calcium resorption with increased urinary calcium excretion, and (3) suppressed osteoblast function and decreased bone formation. Ultimately, renal and intestinal losses of calcium result in the development of secondary hyperparathyroidism, which, in concert with stimulation of parathyroid secretion and an increased sensitivity of bone cells to PTH, produces an increase in bone resorption and bone turnover. Although effective forms of prevention and treatment have not been identified, available information provides a rationale for the use of calcium supplements, maintenance of vitamin D nutrition, and the use of agents that suppress bone resorption and bone turnover. The use of sodium fluoride to stimulate bone formation has not been fully tested in this condition and it remains an investigational agent. Although recent advances in our understanding of the glucocorticoid receptor are likely to lead us to new therapeutic approaches, present methods of prevention and treatment have not been adequately evaluated and await prospective study.

Adrenal Cortex Hormones↗

Efficacy of nonloading exercises in prevention of vertebral bone loss in postmenopausal women: a controlled trial.

A considerable increase in muscle strength and bone mass can be achieved in young adults through athletic exercise programs. We studied a less demanding nonloading exercise program for the back extensor muscles in postmenopausal women who were not on estrogen therapy. We randomly assigned 65 healthy Caucasian women without evidence of or risk factors for osteoporosis into an exercise group and a control group. The strength of the back extensor muscles and bone mineral density of the lumbar spine were measured at baseline and every 6 months for 2 years. In addition, a physical activity score was determined. Compliance was assessed by regular interviews and review of diaries. During the 2-year study, the mean rates of bone loss in the two groups were not statistically different. The strength of the back extensor muscles increased in both groups but significantly more (P = 0.002) in the exercise group. We conclude that postmenopausal bone loss is unaffected by a modest exercise program despite an increase in muscle strength. Nonloading muscle exercise may be ineffective in retarding vertebral bone loss in ambulatory, healthy postmenopausal women.

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Serum bioactive parathyroid hormone in hemodialysis patients.

In 41 hemodialysis patients with bone disease (histological diagnosis with histomorphometric confirmation of PTH activity) results from a serum immunoreactive PTH (iPTH) assay correlated with results from a new serum bioactive PTH (bio-PTH) assay (r = 0.84; P less than 0.001). The serum bio-PTH values correlated well with osteoclast numbers (r = 0.70; P less than 0.001), resorption surfaces (r = 0.55; P less than 0.001), and presence of marrow fibrosis (P less than 0.02). The serum iPTH values also correlated with osteoclast numbers (r = 0.61; P less than 0.001), resorption surfaces (r = 0.47; P less than 0.003), and presence of marrow fibrosis (P less than 0.02). Serum bio-PTH and iPTH values were higher in patients with severe hyperparathyroidism than in other patients. The assays were equally useful in identifying dialysis patients with severe hyperparathyroidism. Patients with osteomalacia or low turnover bone disease had low serum bio-PTH and/or iPTH values. Low bio-PTH values (less than or equal to 3.6 pmol/L) had a sensitivity and a specificity of 93% for osteomalacia or low turnover bone disease. Low bio-PTH values also were useful in identifying those patients with positive aluminum staining in bone. The serum bio-PTH assay was useful in identifying patients with osteomalacia, low turnover bone disease, or aluminum accumulation.

Adult↗

Prediction of properties of fracture callus by measurement of mineral density using micro-bone densitometry.

UNLABELLED: An experiment was designed to determine whether the material properties of fracture callus can be predicted by the measurement of mineral density. Rat tibiae that had a closed fracture were used to obtain uniform specimens of fracture callus at sequential stages of healing. An in vitro indentation test was done and tissue was biopsied, using a trephine, to determine the hardness and calcium content of a standardized area of callus tissue. The hardness of the callus was correlated with the mineral density of the local tissue, which initially had been measured non-invasively with single-photon-based micro-bone densitometry. The progress of differentiation and remodeling of callus was determined by comparative planimetric and microradiographic analyses of tissue. Determinations of density showed a linear correlation with concentrations of a hydroxyapatite equivalent solution (r = 0.997, p less than 0.001), with the ash weight of control specimens of cortical-trabecular bone (r = 0.998, p less than 0.001), and with the calcium content (micrograms per cubic millimeter) of the fracture callus (r = 0.854, p less than 0.001). The hardness of the callus had a non-linear relationship (r = 0.959, p less than 0.005) with the mineral density per volume of tissue, as measured by micro-bone densitometry. CLINICAL RELEVANCE: The appearance of fracture callus on conventional radiographs is an important clinical finding in the assessment of fracture-healing. It is, however, an unreliable predictor of the strength of the union of the fracture. Three-dimensional imaging and quantification of bone mineral provide additional data about the quality and geometry of fracture callus. Our study showed that mineral content per unit of volume is a good index of hardness of the fracture callus. Thus, quantitative imaging may be useful clinically for monitoring fracture-healing.

Animals↗

Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers.

In 12 younger (age, 30-41 yr) and 11 older (age, 55-73 yr) normal women we assessed bone formation rate using multiple methods. Bone formation (mean +/- SE) was higher in the older women than in the younger women, based on measurements of serum bone Gla-protein (1.67 +/- 0.07 vs. 1.14 +/- 0.10 nmol/L; P less than 0.01), serum bone-specific alkaline phosphatase activity (388 +/- 42 vs. 223 +/- 22 nanokatal/L, P less than 0.01), and bone formation rate by histomorphometry of iliac biopsy (31.1 +/- 4.9% vs. 15.1 +/- 2.7%/yr; P less than 0.01), but was similar in the two groups when accretion rates were assessed by calcium kinetics (5.9 +/- 1.0 vs. 7.5 +/- 1.2; P = NS). This latter discrepancy may have been caused by several age-related factors, especially reduced mineralization of completed osteons, and by not correcting for the decrease in total skeletal calcium in the older group. Our data call into question the traditional belief that bone turnover decreases in older women.

Adult↗

Mechanism of acute lower extremity pain syndrome in fluoride-treated osteoporotic patients.

Acute pain in the lower extremity, which has previously been attributed to synovitis or fasciitis, develops in about 15 percent of osteoporotic patients treated with sodium fluoride. This report describes 11 osteoporotic women in whom this syndrome developed while they were being treated with sodium fluoride (mean dose 78 mg per day; range, 60 to 90). [99mTc]Hydroxymethylene diphosphonate scintiscanning showed an increased number of foci of abnormal uptake in the lower extremities (p less than 0.05), when compared with results of scintiscanning in 12 nonsymptomatic osteoporotic women treated with sodium fluoride and 12 osteoporotic women treated with oral calcium carbonate only. The increased uptake was not restricted to the areas of pain. Roentgenography revealed stress microfractures in five of the 11 symptomatic patients. It is concluded that the acute lower extremity pain syndrome during fluoride therapy usually results from intense regional bone remodeling, which may be complicated by stress microfractures.

Aged↗

Outpatient percutaneous biopsy of the iliac crest: methods, morbidity, and patient acceptance.

Bone histology and histomorphometry have become important in the diagnosis and management of metabolic bone disease, but the invasive nature of the biopsy procedure has limited its use. We describe an outpatient technique for obtaining one or more transiliac bone biopsy specimens. Thirty-eight women with osteoporosis, each of whom had sustained one or more spinal compression fractures, underwent two separate bone biopsies during which two 7.5-mm transiliac cores of bone were removed. No morbidity (such as infection or hemorrhage) was encountered. Subjective responses to the level of pain were surveyed by questionnaire. At the time of biopsy, 46% of the study subjects experienced no or only mild discomfort, and 24% judged their pain to be severe. At 16 hours after biopsy, 64% had no or mild pain and 8% experienced severe pain. At 7 days after biopsy, 79% experienced no or mild pain but 9% judged their pain to be severe. In four patients, temporary ambulatory disability occurred but resolved spontaneously in 7 to 10 days. We conclude that the described outpatient bone biopsy procedure is safe, efficient, and generally acceptable to patients.

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Relationship between bone mineral density of spine and strength of back extensors in healthy postmenopausal women.

We determined the bone mineral density of the lumbar spine and the strength of back extensors in 68 healthy postmenopausal Caucasian women. Bone mineral density of the second to fourth lumbar vertebrae was measured by dual-photon absorptiometry, and back extensor strength was determined with use of a strain-gauge dynamometer. The bone mineral density percentile ranged from 2 to 99%, and back extensor strength ranged from 37 to 145 lb. Statistical analysis demonstrated a significant positive correlation (P = 0.004) between bone mineral density and back extensor strength, even when bone mineral density was corrected for age. Bone mineral density was also significantly positively correlated with body weight (P = 0.003), height (P = 0.001), and arm span (P = 0.008). These data suggest that the strength of back muscles may contribute to the bone mineral density of vertebral bodies.

Aged↗

Bone loss and reduced osteoblast function in primary biliary cirrhosis.

The association of bone loss with primary biliary cirrhosis is poorly understood. In 15 premenopausal female patients, only 2 of whom had fractures, mean bone mineral density was reduced at the lumbar spine but not at the midradius or distal radius. Bone loss was not statistically related to the duration or severity of liver disease. Urinary hydroxyproline excretion, an index for bone resorption, was not different from that of 15 age-matched normal women, but the serum concentration of bone Gla-protein (osteocalcin), a specific marker for bone turnover, was decreased (p less than 0.001). Bone histomorphometric examination in 13 patients showed no osteomalacia but a reduced bone formation rate despite normal values for fractional osteoblast-osteoid interface. The substantial early loss of trabecular bone is mediated by a severe reduction in osteoblast function, which may be caused by retained toxic substances associated with cholestasis.

Adult↗

Catecholamine-secreting paraganglioma of the interatrial septum.

A 29-year-old woman was found to have clinical and biochemical evidence of a functioning paraganglioma (pheochromocytoma) five years after the onset of symptoms. Despite extensive investigation of known potential sites of paragangliomas (including laparatomy), the suspected tumor eluded localization. Adrenergic blocking agents controlled her blood pressure but did not affect the other manifestations of catecholamine excess. Ischemic perforation of the colon and refractory gram-negative sepsis resulted in death. At autopsy, a large paraganglioma was found within the heart; the unique tumor location was an important factor in the fatal clinical course.

Adult↗

High-resolution ultrasound-guided percutaneous needle biopsy and intraoperative ultrasonography of a cervical parathyroid adenoma in a patient with persistent hyperparathyroidism.

We present a case of persistent hyperparathyroidism in which high-resolution real-time ultrasonography was used to perform a percutaneous needle biopsy of a parathyroid tumor. Additionally, intraoperative ultrasonography was valuable in the precise localization of the tumor and thereby reduced the need for extensive surgical reexploration.

Adenoma↗

Effect of the fluoride/calcium regimen on vertebral fracture occurrence in postmenopausal osteoporosis. Comparison with conventional therapy.

We assessed the rates of vertebral fracture in patients with postmenopausal osteoporosis. Forty-five patients were not treated (91 person-years of observation); 59 were treated conventionally, with calcium (alone or combined with estrogen) or vitamin D or both (218 years); and 61 were treated with sodium fluoride combined with conventional therapy (251 years). The fracture rate (per thousand person-years) was 834 in untreated patients, 419 in those given calcium with or without vitamin D, 304 in those given fluoride and calcium with or without vitamin D, 181 in those given estrogen and calcium with or without vitamin D, and 53 in those given fluoride, estrogen, and calcium with or without vitamin D. It was reduced in all treatment groups (P less than 0.001 for calcium and P less than 1 x 10(-6) for other combinations); fluoride (one years of treatment) and estrogen (but not vitamin D) independently reduced the rate from that observed with calcium alone (P less than 0.001). The combination of calcium fluoride, and estrogen was more effective than any other combination (P less than 0.001). These results provide grounds for optimism about the efficacy of combinations of available agents with sodium fluoride for fracture in postmenopausal osteoporosis.

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Activation of virilizing adrenal rest tissues by excessive ACTH production. An unusual presentation of Nelson's syndrome.

Nelson's syndrome occurs in 10 to 35 percent of patients treated for Cushing's disease by bilateral adrenalectomy and features an ACTH-producing pituitary tumor and hyperpigmentation. Cortisol-producing testicular tumors activated by markedly elevated ACTH levels have been described in male patients with Nelson's syndrome. We now describe a female patient with Nelson's syndrome who presented with virilization. Abdominal exploration revealed adrenal rest tumors in the paraovarian tissues and adrenal beds. Iodocholesterol scanning gave negative results. This case illustrates the need for follow-up study of patients with bilateral adrenalectomy for Cushing's disease and describes some of the unusual features these patients may present.

Adrenal Cortex Hormones↗

Treatment of primary osteoporosis with fluoride and calcium. Clinical tolerance and fracture occurrence.

Thirty-six patients with primary osteoporosis were treated for up to six years with sodium fluoride, calcium supplements, and, in 24 patients, vitamin D. Major adverse reactions (synovitis, painful plantar fascial syndrome, recurrent vomiting, or anemia) occurred in 15 patients (42%). New vertebral fractures occurred at a rate of 329 fractures per 1,000 years of observation. Almost half of them occurred during the first year of therapy, and they were only one sixth as frequent in 12 patients who had fluoride-induced increased trabeculation on vertebral roentogenograms. Nevertheless, until long-term safety and antifracture efficacy are better established, this regimen should continue to be restricted to investigational use.

Adult↗