Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment.
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PMID:The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). 2227 95

Skull involvement in Paget's disease of bone can lead to neurological symptoms, prompting treatment. Intravenous zoledronic acid (ZA) has emerged as an effective and safe treatment option for patients with Paget's, leading to sustained remission and improved quality of life. A previously untreated 61-year-old female presented with 2-year history of facial asymmetry with progressive hearing impairment. Serum calcium levels were normal with upper normal levels of PTH and low 25OHD levels. Serum alkaline phosphatase was markedly increased and bone scan showed extensive pagetic involvement of the skull. Head CT and MRI revealed hydrocephalus with cerebellar tonsillar herniation, platybasia and basilar invagination. In the absence of clinical signs or symptoms of intracranial hypertension, she was treated with intravenous ZA after 15-day supplementation with calcium and vitamin D. Twelve hours after the infusion, the patient became confused, agitated and disoriented and developed urinary incontinence; cortical sulci became effaced on CT indicating increased intracranial pressure. Over the following days, she developed frank hypocalcemia requiring intravenous calcium infusion and calcitriol. Neurological status returned to normal within 24 h of onset, except for urinary incontinence. Nine months later she remained incontinent and still required calcitriol to maintain normocalcemia. Zoledronic acid is a first-line option for the treatment of Paget's disease, yet there can be complications in particular clinical scenarios such as pagetic hydrocephalus, as seen in this case. Plentiful supplementation of calcium and vitamin D before bisphosphonate therapy is paramount in order to minimize the risk of prolonged post-treatment hypocalcemia.
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PMID:Symptomatic intracranial hypertension and prolonged hypocalcemia following treatment of Paget's disease of the skull with zoledronic acid. 2307 94