Stephen F. Hodgson

Primary hyperparathyroidism. Incidence, morbidity, and potential economic impact in a community.

We examined the incidence and clinical and economic consequences of primary hyperparathyroidism in residents of Rochester, Minn, from 1965 through 1976; 90 cases were found. From January 1, 1965, to June 31, 1974, the average annual incidence was 7.8 +/- 1.2 (mean +/- S.D.) cases per 100,000 population. However, after the introduction of routine measurement of serum calcium, the average annual incidence rose to 51.1 +/- 9.6 cases per 100,000. Even after availability of routine measurement of serum calcium, the annual incidence of primary hyperparathyroidism among persons 39 years of age or younger remained below 10 cases per 100,000. However, the annual incidence increased sharply in persons 40 or more years of age, reaching 188 cases per 100,000 among women 60 years of age and over and 92 cases per 100,000 among men 60 and over. For the last 1.5 years of the study, the average annual age-adjusted incidence of primary hyperparathyroidism was 27.7 +/- 5.8 per 100,000. The frequency of urolithiasis fell from 51 to 4 per cent (P less than 0.001), and the proportion of cases without symptoms or complications of primary hyperparathyroidism rose from 18 to 51 per cent (P less than 0.005). The median charge in 1977 for diagnosis and treatment of primary hyperparathyroidism was

Treatment of postmenopausal osteoporosis with transdermal estrogen.

1700. (N Engl J Med 302:189-193, 1980).

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

OBJECTIVE To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures. DESIGN Double-blind, randomized, placebo-controlled clinical trial lasting 1 year. SETTING Referral-based outpatient clinic. PATIENTS Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis. INTERVENTIONS Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo. MEASUREMENTS Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate. RESULTS Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with -2.6, P less than 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, -0.35 compared with 0.02 nmol/L; P less than 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, -12.9 compared with -6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% CI, 0.16 to 0.95). CONCLUSIONS Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.

Stronger Back Muscles Reduce the Incidence of Vertebral Fractures: A Prospective 10 Year Follow-up of Postmenopausal Women

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.

Bone Loss and Reduced Osteoblast Function in Primary Biliary Cirrhosis

The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.

Survival after the Diagnosis of Hyperparathyroidism: A Population-based Study

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.

Epidemiology and clinical features of osteoporosis in young individuals

BACKGROUND Reports of increased mortality from cardiovascular disease and malignancy in primary hyperparathyroidism have been based primarily on patients who have undergone parathyroidectomy. In order to assess the true impact of primary hyperthyroidism on mortality in the general population, we assessed survival in a large inception cohort of Rochester, Minnesota residents with primary hyperparathyroidism initially diagnosed over a 28-year span, the majority of whom were followed with uncomplicated disease. METHODS All Rochester residents with primary hyperparathyroidism first recognized in 1965 to 1992 were identified through the Rochester Epidemiology Project medical records linkage system. Included as cases were patients with pathologic confirmation of hyperthyroidism, hypercalcemia with inappropriately elevated parathyroid hormone levels, or hypercalcemia for more than a year with no other cause. Survival was estimated using the Kaplan Meier product-limit method. The Cox proportional hazards model was used to determine associations, as relative hazards (RR) with 95% confidence intervals (CI), of various risk factors with time to death. RESULTS During the study period, 435 cases of primary hyperparathyroidism were identified. Altogether, parathyroid surgery was performed on 126 patients (29%), with a mean delay between the initial elevated serum calcium level and surgery of 3.3 years. Patients who underwent surgery had higher maximum serum calcium levels than the patients who were observed (mean+/-SD, 11.3+/-0.7 versus 10.7+/-0.4 mg/dL, P <0.00 1), but their mean ages were similar (54+/-16 versus 56+/-17 years). Overall survival in the patients with primary hyperthyroidism was better than expected (P=0.02), but by age-adjusted multivariate analysis, higher maximal serum calcium level was an independent predictor of mortality (RR=1.3 per mg/dL; 95% CI: 1.1-1.6; P <0.02). CONCLUSION Overall survival is not adversely affected among unselected patients with mild primary HPT in the community, although patients with more severe disease, as manifested by higher serum calcium levels, may have an increased risk of death.

Efficacy of Nonloading Exercises in Prevention of Vertebral Bone Loss in Postmenopausal Women: A Controlled Trial

Due to the lack of epidemiologic data on osteoporosis in the young, we identified all 22 Olmsted County, MN, residents aged 20-44 years when first diagnosed with established osteoporosis in 1976-1990. The overall age- and sex-adjusted incidence rate was 4.1 per 100,000 person-years (95% CI 2.4-5.9) with a female to male ratio of age-adjusted rates of 1.2:1. The majority represented secondary osteoporosis (12 steroid-induced, 3 postmenopausal, 2 delayed puberty, 2 anticonvulsant-induced, 2 gastrointestinal disease, 2 alcoholism, 1 anorexia nervosa, and 7 other etiologies; some individuals had more than one factor present) but two had idiopathic osteoporosis (incidence 0.4 per 100,000 person-years, 95% CI 0-0.9). To further characterize the patients with idiopathic osteoporosis, we also reviewed the entire Mayo Clinic experience with such patients from 1976 to 1990, regardless of residency. A total of 56 patients (30 female/26 male) were identified with a median age at diagnosis of 34 years. Only 8% were hypercalciuric at presentation. There was a preponderance of cancellous bone fractures (vertebral 81%, rib 37%, wrist 13%), although 13% did have hip fractures. Transiliac bone biopsies were available in 18 patients. As compared to age- and sex-matched controls, the osteoporotic subjects had a significant reduction in trabecular bone volume, cortical thickness, and mean wall thickness, the latter suggesting an abnormality in osteoblast function in these individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactase Deficiency: Prevalence in Osteoporosis

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.

Osteomalacia after Roux-en-Y gastric bypass.

We determined the prevalence of lactase deficiency by analysis of respiratory hydrogen (H2) in 30 women with idiopathic postmenopausal osteoporosis and in 31 female control subjects without evidence of metabolic bone disease. Eight subjects with osteoporosis had breath H2 excretion greater than 0.20 ml/minute at 2 h after receiving 50 g of lactose and were considered lactase deficient; only one control subject was lactase deficient (P less than 0.05). Symptoms developed in seven of the nine lactase-deficient persons after receiving 50 g of lactose; in contrast, only three of the 52 lactase-normal subjects had symptoms. Although none of the lactase-deficient subjects was aware of milk intolerance, their intake of both lactose and calcium was significantly lower than that in the lactase-normal group. Lactase deficiency appears to be one of several factors that predispose to the development of osteoporosis, probably through diminished calcium intake and possibly through an effect on calcium absorption.