Does a diabetes annual review make a difference?

AIMS: To determine whether a diabetes annual review, independently of other care processes, is followed by improved patient clinical measurements. METHODS: Audits conducted independently of the diabetes annual review were analysed for a time-trend in patient clinical measures. An interaction variable between the review and the year of audit was used to test for a change in gradient before and after a diabetes annual review. Each patient formed their own control. RESULTS: The data included 9471 audits on 3397 patients from 92 practices, and diabetes annual reviews from 2003 to mid-2008. Percentages of patients with raised HbA(1c) , systolic blood pressure and lipids improved from first to last audit. Predicted means after a diabetes annual review for HbA(1c) decreased by 0.13% (1.0 mmol/mol), for HDL cholesterol increased by 0.04 mmol/L and for triglyceride decreased by 0.2 mmol/L. Predicted systolic and diastolic blood pressure, total cholesterol and urinary albumin:creatinine ratio did not change significantly. CONCLUSIONS: Metabolic control improved over time but this was largely independently of the diabetes annual review, which appears to add little clinical value to existing New Zealand general practice care processes. Currently, general practitioners are paid to undertake a diabetes annual review and report the measurements collected. We would argue that payment needs to be directed to demonstrating appropriate changes in clinical management or achieving meaningful clinical goals, and that the annual review results should be part of systematic feedback to general practitioners, particularly directed at clinical inertia.

Thyrotoxic, hypokalaemic periodic paralysis: Polynesians, an ethnic group at risk.

BACKGROUND: Thyrotoxic, hypokalaemic periodic paralysis (TPP) is a reversible cause of severe muscle weakness that occurs in a small minority of thyrotoxic patients. Most cases to date have been reported in Asian men. AIMS: To evaluate the ethnic distribution of patients with TPP. METHODS: Retrospective analysis of all patients presenting with thyrotoxicosis and hypokalaemia with paralysis to two New Zealand hospitals. RESULTS: Seventy-one per cent of the 21 patients with TPP were of Polynesian ethnicity (Maori and Pacific Islander), 24% Asian and 5% European. Based on population demographics, these figures suggest a 37-fold overrepresentation for Polynesians and 159-fold for Asians compared with New Zealand Europeans. CONCLUSION: Polynesian, in addition to Asian people, are two ethnic groups at particular risk of TPP, and this condition must be considered in the differential diagnosis for patients presenting to the emergency department with severe hypokalaemia and weakness.

The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women.

SUMMARY: We performed a 2-year extension of our previous 2-year randomized controlled trial of the effects of hydrochlorothiazide on bone mineral density. The improvements in bone density seen in the first 2 years were sustained throughout the extension study. Thiazides provide a further option in the prevention of postmenopausal bone loss. INTRODUCTION: Thiazide diuretics reduce urinary calcium excretion and therefore might prevent osteoporosis. Previously we reported a 2-year randomized controlled trial of hydrochlorothiazide treatment in 185 postmenopausal women that showed positive benefits of hydrochlorothiazide on bone density. Here, we report the results of a 2-year extension to that study. METHODS: Of 185 healthy postmenopausal women, 122 agreed to continue in a double-blinded 2-year extension taking 50 mg hydrochlorothiazide or placebo daily. Measurements of bone density occurred every 6 months and of calcium metabolism at 2 and 4 years. RESULTS: The improvements in bone density seen in the first 2 years of the trial were sustained throughout the extension. There were significant between-groups differences in the change in bone density over 4 years at the total body (0.9%, P<0.001), legs (1.0%, P=0.002), mid-forearm (1.1%, P=0.03), and ultradistal forearm (1.4%, P=0.04). At the lumbar spine (0.9%, P=0.76) and femoral neck (0.4%, P=0.53) the between-groups differences did not reach statistical significance. CONCLUSIONS: Hydrochlorothiazide produces small positive benefits on cortical bone density that are sustained for at least the first 4 years of treatment. They provide a further option in the prevention of postmenopausal bone loss, especially for women with hypertension or a history of kidney stones.

Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial.

PURPOSE: Thiazide diuretics reduce urine calcium excretion and might therefore reduce postmenopausal bone loss. In some, but not all, case-control studies, their use has been associated with a reduced incidence of hip fractures. We studied the effects of hydrochlorothiazide on bone loss in normal postmenopausal women. SUBJECTS AND METHODS: We performed a randomized, double-blind, 2-year trial of the effects of hydrochlorothiazide (50 mg per day) and placebo on bone mineral density in normal postmenopausal women. Participants were not required to have either low bone mineral density or hypertension. Bone mineral density was measured using dual-energy x-ray absorptiometry. RESULTS: One hundred eighty-five women entered the study, of whom 138 completed 2 years of follow-up. In an intention-to-treat analysis, hydrochlorothiazide produced significant benefits on bone mineral density of the total body (between-group difference at 2 years of 0.8%, 95% confidence interval [CI]: 0.3% to 1.3%, P <0.0001), legs (0.9%, 95% CI: 0.2% to 1.7%, P <0.0001), mid-forearm (1.2%, 95% CI: 0.2% to 2.2%, P = 0.02), and ultradistal forearm (1.7%, 95% CI: 0.1% to 3.2%, P = 0.04). There was no effect in the lumbar spine (0.5%, 95% CI: -0.5% to 1.6%) or femoral neck (0.2%, 95% CI: 1.3% to 1.7%). The between-group changes tended to be greatest during the first 6 months, except in the mid-forearm where there appeared to be a progressive divergence. An as-treated analysis produced similar results. Urine calcium excretion and indices of bone turnover decreased in the thiazide group, but parathyroid hormone concentrations did not differ between the groups. Treatment was tolerated well. CONCLUSIONS: Hydrochlorothiazide (50 mg per day) slows cortical bone loss in normal postmenopausal women. It may act directly on bone as well as on the renal tubule. The small size of the effect suggests that thiazides may have a role in the prevention of postmenopausal bone loss, but that they are not an appropriate monotherapy for treating osteoporosis.

Effects of hormone replacement therapy on bone mineral density in postmenopausal women with primary hyperparathyroidism: four-year follow-up and comparison with healthy postmenopausal women.

BACKGROUND: Long-term treatment of patients with asymptomatic primary hyperparathyroidism remains controversial, but the presence of osteoporosis is regarded as an indication for parathyroidectomy. Hormone replacement therapy (HRT) is a possible alternative therapy in osteopenic postmenopausal women with the disorder, and results of short-term studies suggest a beneficial effect on bone mass comparable to that achieved by parathyroidectomy. Longer-term data are required to further assess the efficacy of this treatment in chronic stable primary hyperparathyroidism. METHODS: We report the results of the extension from 2 to 4 years of a randomized, placebo-controlled trial of HRT in postmenopausal women with primary hyperparathyroidism. Of 23 postmenopausal women with primary hyperparathyroidism, 11 received active HRT with conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 5 mg/d, and 12 received placebo. Bone mineral density was measured throughout the skeleton at 6-month intervals using dual-energy x-ray absorptiometry in these women and in 50 normocalcemic age-matched control subjects. None of the 23 patients withdrew during the extension period. RESULTS: Changes in bone mineral density were more positive in those taking HRT than placebo, with the between-group differences at 4 years being 4.6% in the total body, 7.5% in the lumbar spine, 7.4% in the femoral neck, 8.2% in the femoral trochanter, 6.8% in the legs, and 7.0% in the forearm (P<.01). At skeletal sites composed predominantly of cortical bone, there was a progressive divergence of the 2 groups. Biochemical markers of bone turnover remained lower throughout the study in women taking HRT. When rates of bone loss were compared between the placebo group and healthy women of comparable age, bone loss tended to be more marked throughout the skeleton in women with hyperparathyroidism, but only in the total body and its legs subregion was this difference significant. CONCLUSIONS: Hormone replacement therapy is efficacious in the long-term management of osteopenia in postmenopausal women with primary hyperparathyroidism and thus represents an important new therapeutic option for asymptomatic patients who do not have other indications for surgery. Bone loss seems to be accelerated in untreated primary hyperparathyroidism.

Hormone replacement therapy causes a respiratory alkalosis in normal postmenopausal women.

Menopause is associated with an increase in venous bicarbonate concentrations that is reversible with hormone replacement therapy (HRT). However, the mechanism underlying this effect is not known. To address this question, we studied the changes in acid-base indexes in the arterialized venous blood of normal postmenopausal women commencing conjugated equine estrogen (0.625 mg/day), medroxyprogesterone acetate (MPA; 5 mg/day), their combination, or placebo, in a double blind randomized controlled study over 3 months. Serum bicarbonate concentrations decreased significantly in the groups receiving either MPA or estrogen plus MPA (P = 0.008). This trend was apparent as early as 2 days and reached 2.7 and 2.3 mmol/L in the respective groups by 3 months. Similar changes were seen with partial pressure of carbon dioxide (P = 0.04); a change of -0.7 kPa occurred in the estrogen plus MPA group at 3 months. There were no changes in bicarbonate concentrations or partial pressure of carbon dioxide in those receiving estrogen alone or placebo. Accompanying changes in blood pH were apparent in the estrogen plus MPA group, where there was an upward trend at 1 week (P = 0.056) and a significant change from baseline (+0.013) at 3 months (P = 0.03). In the whole group, the changes in pH were inversely correlated with those in urinary excretion of hydroxyproline (r = -0.44; P = 0.01). We conclude that HRT using conjugated estrogens and MPA produces small, but sustained, changes in acid-base status. These may contribute to the effects of HRT and menopause on many tissues and disease processes, including the development of osteoporosis.

The effect of past use of the injectable contraceptive depot medroxyprogesterone acetate on bone mineral density in normal post-menopausal women.

OBJECTIVE: Depot medroxyprogesterone acetate (DMPA), an injectable progestogen, is a widely used contraceptive acting primarily by inhibiting secretion of pituitary gonadotrophins, thus producing oestrogen deficiency. Cross-sectional and prospective studies in pre-menopausal women have shown DMPA use to be associated with reduced bone density, but bone density increases following discontinuation of the drug. Because fracture rates are low in pre-menopausal women, the principal concern arising from the effects of DMPA on bone is that there may be residual osteopenia in former users such that their post-menopausal fracture risk is increased. The present study addresses this question. DESIGN: Cross-sectional study of bone density in post-menopausal former users of DPMA and controls. SUBJECTS: Three hundred and forty-six normal post-menopausal women, of whom 34 had previously used DMPA. The median age at which DMPA use began was 41 years and the median duration of use was 3.0 years. MEASUREMENTS: Bone density was measured in the spine, proximal femur and total body by dual-energy, X-ray absorptiometry. RESULTS: There were no significant differences in bone density at any site between the women who had previously used DMPA and the others in the cohort. However, in those who had used DMPA for > 2 years there was a trend towards bone densities being lower in the former users, the differences from non-users being 1.6% in the lumbar spine (P = 0.6), 3.1% in the femoral neck (P = 0.4) and 0.5% in the total body (P = 0.8). There was no correlation between bone densities and the duration of DMPA use, the age at discontinuation of DMPA, or the time between DMPA discontinuation and the menopause. CONCLUSIONS: Any residual effects of depot medroxyprogesterone acetate use on post-menopausal bone density are small and therefore unlikely to have a substantial impact on fracture risk in the post-menopausal years.

PIP: The possibility that use of depot medroxyprogesterone acetate (DMPA) has residual effects on postmenopausal bone mineral density was assessed in a cross-sectional study of 346 postmenopausal former users of DMPA and controls from Auckland, New Zealand. 34 women (10%) reported past use of DMPA, for a median duration of 3 years, starting at a median age of 41 years. Dual-energy, x-ray absorptiometry failed to reveal significant differences between past users of DMPA and never-users in bone density in the spine, proximal femur, or total body. However, in women who had used DMPA for more than 2 years, there was a nonsignificant trend toward lower bone densities in former users compared with never-users. The difference between mean measurements was 1.6% in the lumbar spine (p = 0.6), 3.1% in the femoral neck (p = 0.4), and 0.5% in the total body (p = 0.8). There was no correlation between bone densities and the duration of DMPA use, age at discontinuation of DMPA use, or the time between DMPA discontinuation and menopause. These findings suggest that any residual effects of DMPA use on postmenopausal bone density are likely to be small and without a substantial impact on fracture risk.

Premature hair graying and bone mineral density.

In a recent case-control study, premature hair graying was found to be associated with osteopenia, suggesting that this might be a clinically useful risk factor for osteoporosis. We report a reexamination of this possibility in 293 healthy postmenopausal women. Subjects experiencing onset of hair graying in their 20s tended to have lower bone mineral density throughout the skeleton (adjusted for age and weight) than those with onset of graying later in life. The same was true for those in whom the majority of their hair was gray by the age of 40 yr (n = 16), in whom bone density was reduced by 7% in the femoral neck, 8% in the femoral trochanter, and 4% in the total body (P < 0.05) when compared with those not prematurely gray. Bone density at the lumbar spine and Ward's triangle showed similar trends that were not significant. However, premature hair graying explained only 0.6-1.3% of the variance in bone mineral density within the population. We conclude that premature hair graying is associated with low bone density, but that its infrequency in the normal postmenopausal population leads to its accounting for only a tiny fraction of the variance of bone density.

Effects of prolonged bisphosphonate therapy and its discontinuation on bone mineral density in post-menopausal osteoporosis.

OBJECTIVE: The bisphosphonates have proven efficacy in the management of post-menopausal osteoporosis. However, the benefits of prolonged (> 2 years) administration and the effects of discontinuation of bisphosphonate treatment are not clear. DESIGN: We have previously reported a 2-year, randomized, double-blind, placebo-controlled trial of pamidronate therapy (150 mg/day) in women with established post-menopausal osteoporosis. We now report the bone mineral density (BMD) changes in those women who continued for a third year of active treatment and were then observed off therapy for a further 12 months. PATIENTS: Twenty-two women (mean age 66 years) continued on pamidronate in year 3, and in 16 of these the effects of subsequent discontinuation of therapy for 12 months were studied. MEASUREMENTS: BMD was measured in the total body, lumbar spine and proximal femur using a Lunar DPX-L dual-energy, X-ray absorptiometer. RESULTS: The third year of therapy with pamidronate was associated with a significant further gain in BMD only at the lumbar spine (2.1 +/- 0.6%, P = 0.003), resulting in a total gain of 9.5 +/- 1.0% at that site over 3 years of treatment. In the total body, BMD tended to decline (-0.6 +/- 0.3%) in year 3. One year after discontinuation of pamidronate, there were significant losses of BMD in the total body (-1.9 +/- 0.3%, P < 0.0001) and femoral trochanter (-2.7 +/- 0.9%, P = 0.01), and non-significant changes at the lumbar spine (-0.9 +/- 0.8%), femoral neck (-0.5 +/- 1.6%), and Ward's triangle (-2.9 +/- 3.7%). By the end of one year off therapy, BMD was greater than baseline only in the lumbar spine (7.1 +/- 1.1%, P < 0.0001) and femoral trochanter (4.5 +/- 1.88%, P < 0.03). In the total body, BMD was 0.3 +/- 0.7% below the values at the trial's inception (P = 0.7). CONCLUSIONS: These data demonstrate that the rate of bone gain associated with bisphosphonate use slows over time, and that significant bone loss follows withdrawal of these agents. These findings have important implications for the duration of use of these novel drugs in the therapy of osteoporosis and suggest a need for close observation following their discontinuation.

High peripheral and axial bone densities in a postmenopausal woman with untreated hypoparathyroidism.

It has been reported that bone density is increased in patients with treated hypoparathyroidism, though it is unclear whether this increase is attributable to the condition itself or to its treatment. We have recently investigated a 70 year old woman with untreated hypoparathyroidism from the time of thyroid surgery at the age of 29 years. Bone mineral content of the non-dominant distal forearm was 3.7 standard deviations above the mean normal value found in 23 healthy volunteers of comparable menopausal age, and was also above the mean normal value found in premenopausal women. The vertebral mineral density of her lumbar spine (measured by quantitative computed tomography) was 3.0 standard deviations above the mean normal value. These findings suggest that high bone density is a feature of hypoparathyroidism per se and that postmenopausal bone loss may be significantly attenuated in this condition.