Current perspectives on bisphosphonate treatment in Paget’s disease of bone

Winnie Zee Man Wat Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong Abstract: Paget’s disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget’s disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget’s disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget’s disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget’s disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its associated risk of malignancy. Keywords: osteitis deformans, antiresorptive, alkaline phosphatas

Prevalence and impact of vitamin D insufficiency in Southern Chinese adults

Introduction: Vitamin D is a vital element for bone health but the problem of vitamin D deficiency is underestimated in Hong Kong. Methods: Serum 25(OH)D and parathyroid hormone (PTH) levels were evaluated in 382 community dwelling Chinese adults >50 years for their relation with bone mineral density (BMD) and risks of osteoporotic fractures and falls. Results: The mean age of the subjects was 69 ± 9 years. The mean 25(OH)D level was 28.3 ± 10.8 ng/ml with 62.8% of the subjects having levels <30 ng/ml. 6.3% of the subjects had elevated PTH levels. A curvilinear relation between serum PTH and 25(OH)D was found, with PTH starting to increase when 25(OH)D level fell below 30 ng/ml (r = -0.233, p < 0.05). Although subjects with vitamin D <30 ng/ml had significantly lower BMD, only sex, age and PTH but not 25(OH)D were predictors of BMD at the spine and hip. Subjects with elevated PTH levels had a 2.92-fold increased risk of falls and 2.94-fold increased risk of fractures at the hip and spine. Conclusions: Vitamin D insufficiency and its complication of secondary hyperparathyroidism is common even in subtropical region and is an important risk factor for low bone mass, falls and fractures. Copyright © 2007 S. Karger AG.link_to_subscribed_fulltex

Global vitamin D status and determinants of hypovitaminosis D

The aim of the study was to compare the structural and functional parameters of the myocardium in different genotypes of polymorphic markers BsmI (B/b) (rs1544410) and FokI (F/f) (rs2228570) of the vitamin D receptor gene (VDR) in individuals with cardiovascular diseases (CVD). Materials and Methods. We examined 198 patients with CVD. BsmI and FokI of the VDR gene were determined by the polymerase chain reaction. The blood levels of parathyroid hormone, 25(OH)D total, endothelin-1, plasma renin activity were revealed by the method of enzyme immunoassay. The calcium and phosphorus level in the blood was defined by the colorimetric method. Echocardiography was performed by GE Logic P5 Premium (Korea) with a phased sector sensor with a frequency of 2–4 MHz in the modes M-, B-, PW, CW. Results. All participants were divided into groups according to genotypes of FokI and BsmI of the VDR gene. For each polymorphism, the groups were comparable in age, CVD, blood pressure, heart rate, body mass index and levels of the estimated biomarkers. Significant differences (p &lt; 0.05) in the sizes of the aorta and the left atrium (LA), in the sizes and volumes of the left ventricle (LV) and its walls, the diameter of the LV outlet tract and the ejection fraction between the groups with the genotypes of FF and ff were established. In addition, differences (p &lt; 0.05) were found in the aorta size, LA and interventricular septum between the groups with the genotypes of ff and Ff. According to the genotypes of BsmI of the VDR gene, the groups did not differ significantly in the estimated structural and functional parameters of the myocardium and aorta. Hypertrophy of the LV is diagnosed in 78.6 % of participants. Conclusions. Polymorphism of FokI, but not of BsmI of the VDR gene is associated with structural and functional parameters of the myocardium and aorta in individuals with CVD in the Grodno region of Belarus. With the greatest frequency, LV hypertrophy occurs with Ff (37.9 %) and Bb (33.8 %).Цель исследования – сравнение структурно-функциональных показателей миокарда при разных генотипах полиморфных маркеров BsmI (B/b) (rs1544410) и FokI (F/f) (rs2228570) гена рецептора витамина D (VDR) у лиц с сердечно-сосудистыми заболеваниями (ССЗ). Материалы и методы. Обследовано 198 пациентов с ССЗ. Определение BsmI и FokI гена VDR проводили методом полимеразной цепной реакции. Содержание в крови паратиреоидного гормона, 25(OH)D общего, эндотелина-1, активность ренина плазмы определяли методом иммунофер- ментного анализа. Определение в крови уровня кальция и фосфора проводилось колориметрическим методом. Эхо- кардиография выполнялась аппаратом GE Logic P5 Premium (Корея) фазированным секторным датчиком с частотой 2–4 мГц в режимах М-, В-, PW, CW. Результаты. Все обследованные были разделены на группы по генотипам FokI и BsmI гена VDR. При каждом полиморфизме группы были сопоставимы по возрасту, ССЗ, значениям артериального давления, частоте сердечных сокращений, индексу массы тела и уровням оцененных биомаркеров. Установлены достоверные (p &lt; 0,05) отличия по размерам отделов аорты, левого предсердия (ЛП), размерам и объемам левого желудочка (ЛЖ) и его стенок, диаметром выходного тракта ЛЖ и фракцией выброса между группами с генотипом FF и ff. Кроме того, установлены отличия (p &lt; 0,05) по размерам отделов аорты, ЛП и толщиной межжелудочковой перегородки между группами с генотипом ff и Ff. По генотипам BsmI гена VDR группы достоверно не отличались по оцененным структурно-функциональным показателям миокарда и аорты. Гипертрофия ЛЖ диагностирована у 78,6 % обследованных. Заключение. Полиморфизм FokI, но не BsmI гена VDR ассоциирован со структурно-функциональными показателями миокарда и аорты у лиц с ССЗ у жителей Гродненского региона Беларуси. С наибольшей частотой гипертрофия ЛЖ встречается при Ff (37,9 %) и Bb (33,8 %) генотипах.