Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

Management of osteoporosis in patients hospitalized for hip fractures.

Hip fracture is associated with high morbidity, mortality, and economic burden worldwide. It is also a major risk factor for a subsequent fracture. A literature search on the management of osteoporosis in patients with hip fracture was performed on the Medline database. Only one clinical drug trial was conducted in patients with a recent hip fracture. Further studies that specifically address post-fracture management of hip fracture are needed. The efficacy of anti-osteoporosis medication in older individuals and those at high risk of fall is reviewed in this paper. Adequate nutrition is vital for bone health and to prevent falls, especially in malnourished patients. Protein, calcium, and vitamin D supplementation is associated with increased hip BMD and a reduction in falls. Fall prevention, exercise, and balance training incorporated in a comprehensive rehabilitation program are essential to improve functional disability and survival. Exclusion of secondary causes of osteoporosis and treatment of coexistent medical conditions are also vital. Such a multidisciplinary team approach to the management of hip fracture patients is associated with a better clinical outcome. Although hip fracture is the most serious of all fractures, osteoporosis management should be prioritized to prevent deterioration of health and occurrence of further fracture.

The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in osteoporotic Chinese women: a randomized placebo-controlled study.

Osteoporosis has become an important health problem in postmenopausal Asian populations as the prevalence of hip and vertebral fractures in some Asian countries has risen to approach that of Caucasian populations. Risedronate, a pyridinyl-bisphosphonate agent, is a potent inhibitor of bone resorption. Risedronate increases bone mineral density (BMD), reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. To determine the efficacy and tolerability of risedronate in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in Hong Kong. Sixty-five (65) postmenopausal osteoporotic Southern Chinese women, aged 67+/-6 years, were randomly assigned to receive either risedronate 5 mg daily (n=31) or placebo (n=34) for 12 months. All women received calcium carbonate 500 mg daily and vitamin D 400 IU daily. Mean baseline BMD T-score at the spine and total hip was -3.4 and -2.6, respectively. A significant increase in spine BMD was already evident at month 3 of risedronate treatment (P<0.001). Risedronate significantly increased BMD and reduced bone turnover markers as compared with placebo. The risedronate group had significant increase in BMD at 12 months at both the spine and hip when compared with the placebo group (L1-4 6.6% vs. 0.4%, P<0.001; total hip 2.7% vs. 0.3, P<0.0001; femoral neck 1.8% vs. 1.1%, P<0.02; trochanter 4% vs. 1.1%, P<0.0001, respectively). Significant changes in urine N-telopeptide (NTx) and serum osteocalcin were evident as early as 1 and 3 months, respectively, with risedronate treatment. No significant changes were seen in both BMD and bone markers in the placebo group. Risedronate was well tolerated without major adverse effects. We conclude that risedronate is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Asian population.

Acarbose in NIDDM patients with poor control on conventional oral agents. A 24-week placebo-controlled study.

OBJECTIVE: To determine the efficacy of acarbose, compared with placebo, on the metabolic control of NIDDM patients inadequately controlled on maximal doses of conventional oral agents. RESEARCH DESIGN AND METHODS: In this three-center double-blind study, 90 Chinese NIDDM patients with persistent poor glycemic control despite maximal doses of sulfonylurea and metformin were randomly assigned to receive additional treatment with acarbose 100 mg thrice daily or placebo for 24 weeks, after 6 weeks of dietary reinforcement. Efficacy was assessed by changes in HbA1c, fasting and 1-h postprandial plasma glucose and insulin levels, and fasting lipid levels. RESULTS: Acarbose treatment was associated with significantly greater reductions in HbA1c (-0.5 +/- 0.2% vs. placebo 0.1 +/- 0.2% [means +/- SEM], P = 0.038), 1-h postprandial glucose (-2.3 +/- 0.4 mmol/l vs. placebo 0.7 +/- 0.4 mmol/l, P < 0.001) and body weight (-0.54 +/- 0.32 kg vs. placebo 0.42 +/- 0.29 kg, P < 0.05). There was no significant difference between the two groups regarding changes in fasting plasma glucose and lipids or fasting and postprandial insulin levels. Flatulence was the most common side effect (acarbose vs. placebo: 28/45 vs. 11/44, P < 0.05). One patient on acarbose had asymptomatic elevations in serum transaminases that normalized in 4 weeks after acarbose withdrawal. Another patient on acarbose developed severe hypoglycemia; glycemic control was subsequently maintained on half the baseline dosage of sulfonylurea. CONCLUSIONS: In NIDDM patients inadequately controlled on conventional oral agents, acarbose in moderate doses resulted in beneficial effects on glycemic control, especially postprandial glycemia, and mean body weight. Additional use of acarbose can be considered as a useful alternative in such patients if they are reluctant to accept insulin therapy.

Do androgens regulate growth hormone-binding protein in adult man?

To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.

Changing prevalence of retinopathy in newly diagnosed non-insulin dependent diabetes mellitus patients in Hong Kong.

In this retrospective study, the prevalence of chronic microangiopathic complications was determined in 474 Chinese patients with non-insulin dependent diabetes mellitus (NIDDM) who presented within 1 year of diagnosis to the diabetes clinic from January 1990 to December 1996. Mean age (+/- S.E.) was 53.6 (+/- 0.6) years. The overall prevalence of retinopathy was 21.9%. A significant increase was observed from 1990 to 1994 (P < 0.005), with the prevalence being 14.8, 13.0, 24.5, 32.3 and 35.4%, respectively, in consecutive years. A decreasing prevalence was seen from 1994 to 1996 (P < 0.001), being 8.2 and 7.4% in 1995 and 1996, respectively. A total of 95% of patients had nonproliferative retinopathy--proliferative retinopathy was found in 5% only. The overall prevalence of clinical nephropathy (proteinuria > 0.5 g/day) was 3.7%. Clinical neuropathy (increased vibration perception threshold) was found in 12.8% of patients. Patients with retinopathy and neuropathy were older (P < 0.0001 and P < 0.005, respectively) than those without the complications and systolic hypertension was more prevalent in patients with retinopathy (P < 0.05). In conclusion, a high prevalence of diabetic microangiopathic complications, especially of retinopathy, is present in newly diagnosed NIDDM patients in our population. It remains to be determined whether the changing prevalence of retinopathy at diagnosis bears any relationship to the increasing public awareness of diabetes and its complications in Hong Kong in recent years. Examination for chronic microangiopathic complications should be carried out in all newly diagnosed NIDDM patients.

Consensus statement on iodine deficiency disorders in Hong Kong.

This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.

Phaeochromocytoma with adult respiratory distress syndrome mimicking septicaemic shock.

Phaeochromocytomas are rare tumours that most commonly present with chronic sustained hypertension and hypertensive paroxysms or crises. We report a 49-year-old woman with unsuspected phaeochromocytoma who presented with sudden onset of profound hypotension and adult respiratory distress syndrome unresponsive to fluid and inotropic support. This case illustrates the diversity of presentations of phaeochromocytoma, depending on the type and amount of catecholamines secreted.

Awareness of osteoporosis among physicians in China.

Epidemiological studies have projected a vast increase in osteoporotic fractures in Asia, with the majority occurring in China. Awareness of osteoporosis among medical professionals and the pattern of management in Asia have not been explored. A total of 504 doctors in Hong Kong, China with their self-reported practice likely to receive clients with or at risk of osteoporosis were invited to complete a postal questionnaire on the diagnosis and management of their osteoporotic patients. In all, 204 questionnaires were returned, with a response rate of 41%. Only 76% of the respondents reported treating osteoporosis patients in their practice. Ninety-one percent believed that osteoporosis was under-diagnosed. The asymptomatic nature of the disease (66%), inaccessibility (45%) and high cost (54%) of the diagnostic tools were considered major reasons for under-diagnosis. DXA was employed for diagnosis by only 53% of the doctors. Peripheral machines such as ultrasound and quantitative computed tomography were used by 35% of the responders as the only diagnostic tool, especially among clinic-based doctors (clinic-based physicians 47%, hospital-based physicians 17%; P<0.001). Thirty-three percent of the surveyed doctors were unaware of published guidelines for bone mineral density (BMD) measurements. Concerning treatment goals, 82% considered prevention of future fractures and 66% believed improvement in the quality of life of patients as critical or highly important, whereas only about half of the doctors thought that increase in BMD was important. On the other hand, 60% of the doctors considered the cost of therapy a critical or highly important element in the management of osteoporosis. This study showed that physicians in Hong Kong were aware of osteoporosis, though the disease was still under-diagnosed due to inaccessibility and high cost of the diagnostic tools and therapeutic agents. These findings stress the importance of expanding efforts to increase knowledge and awareness among health care providers and also provide future directions for developing strategies for managing osteoporosis in developing Asian regions.

Giant growth-hormone secreting pituitary tumour with extracranial extension.

A 19 year old female patient with typical features of acromegaly was found to have an extensive pituitary tumour with suprasellar, lateral and inferior extensions. Magnetic resonance imaging (MRI) also showed a portion of the tumour extending from the right cavernous sinus through the foramen ovale to become extracranial. Serum growth hormone (GH) was 52.6 mU/L basally and remained elevated after oral glucose, confirming the diagnosis of acromegaly. Treatment with the long-acting somatostatin analogue, octreotide, for 6 months led to a 30% reduction in tumour volume of the intracranial portion but no effect on the extracranial and sphenoidal extensions. She was subsequently treated with trans-sphenoidal surgery followed by external irradiation. The possibility of perineural spread of the tumour was considered.

Pharmacokinetics, pharmacodynamics, long-term efficacy and safety of oral 1-deamino-8-D-arginine vasopressin in adult patients with central diabetes insipidus.

1. The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1-deamino-8-D-arginine vasopressin (DDAVP) were compared in 10 Chinese adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics of commonly used oral preparations (containing 100, 200 and 400 micrograms per tablet) and a 1 year prospective evaluation of the long-term safety and efficacy of oral DDAVP. 2. Following 20 micrograms IN and 200 micrograms orally, respective plasma DDAVP concentrations peaked after 45.6 +/- 7.3 and 93.3 +/- 3.3 (mean +/- s.e.mean) min, reaching 24.1 +/- 4.7 and 15.1 +/- 3.2 pmol 1(-1) and respective terminal half-lives were 2.2 +/- 0.1 and 2.0 +/- 0.1 h. Based on the area under the concentration-time-curve, the bioequivalent IN/oral ratio was 1:16. 3. As judged by changes in urine flow rate and osmolality after IN or oral (100, 200 or 400 micrograms) DDAVP, antidiuretic activity increased rapidly during the second hour and peaked at 4 h. The antidiuresis duration and magnitude correlated with the oral dose (P < 0.001 and < 0.05 respectively), and was least following 100 micrograms (P < 0.01 vs 200 or 400 micrograms). Increasing the dose from 200 to 400 micrograms did not increase maximal antidiuretic activity significantly, but there was a trend towards a longer duration of action (P = 0.076). 4. During the 1-year prospective study with oral DDAVP 300-600 micrograms per day in two to three doses, stable and satisfactory antidiuresis (comparable with that on previous IN therapy) was maintained; tablets were well-tolerated and no side-effect warranted drug withdrawal. 5. These findings suggest that the 100 and 200 micrograms preparations of oral DDAVP are adequate for the long-term control of central diabetes insipidus in our population, and that the 400 micrograms preparation may have a role if the frequency of administration is to be reduced.