Renal Hypophosphatemic Rickets: Growth Acceleration After Long-Term Treatment with 1,25-Dihydroxyvitamin-D3

PEDIATRICS ◽  
1980 ◽  
Vol 66 (3) ◽  
pp. 445-454 ◽  
Author(s):  
James C. M. Chan ◽  
Robert D. Lovinger ◽  
Peter Mamunes
Keyword(s):  
Serum Alkaline Phosphatase ◽  
Bone Age ◽  
Term Treatment ◽  
Hypophosphatemic Rickets ◽  
Phosphorus Concentration ◽  
Calcium Excretion ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Long Term Treatment

Treatment with 1,25-dihydroxyvitamin-D3 and phosphorus supplementation for as long as 48 months was evaluated in six patients with renal hypophosphatemic rickets. Previous phosphorus supplementation of 1,800 to 4,000 mg/sq m of body surface area per day was continued while 1,25-dihydroxyvitamin-D3 at 17 to 80 ng/kg of body weight per day was given orally in place of vitamin-D2. The serum calcium concentration stayed within the normal range in the majority of patients, while the serum phosphorus concentration rose from 2.5 ± 0.4 to 3.4 ± 1.2 mg/100 ml after one month (P < .01). With rare exceptions, serum alkaline phosphatase and parathyroid hormone concentrations stayed normal throughout the study. Healing of rickets was demonstrated by radiography. In five patients, growth velocity was evaluated for 12 months before and after therapy. Growth accelerations were 123% to 235% of that expected for changes in chronologic age and 114% to 200% expected for changes in bone age after therapy. Orally administered, 1,25-dihydroxyvitamin-D3 increased renal calcium excretion and calcium retention was achieved by virtue of the decreased fecal calcium loss. In contrast, 1,25-dihydroxyvitamin-D3, even at doses up to 4 µg/day (80 ng/kg/day) did not significantly alter renal phosphaturia. The phosphorus retention was therefore achieved as the result of the decreased fecal phosphate excretion. The absence of hypercalcemia even at high doses of 1,25-dihydroxyvitamin-D3 and the enhanced linear growth support the long-term therapeutic value of 1,25-dihydroxyvitamin-D3 in renal hypophosphatemic rickets.

Effect of a long-term treatment with 1,25-dihydroxyvitamin D3 on osteocalcin in postmenopausal osteoporosis

1986 ◽  
Vol 38 (6) ◽  
pp. 328-332 ◽  
Author(s):  
A. Caniggia ◽  
R. Nuti ◽  
M. Galli ◽  
F. Loré ◽  
V. Turchetti ◽  
...  
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Term Treatment ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Long Term Treatment

LONG-TERM TREATMENT OF DWARFISM WITH ANDROGENS AND THYROID HORMONE

1959 ◽  
Vol XXXII (IV) ◽  
pp. 563-574 ◽  
Author(s):  
H. Hortling ◽  
K. Wahlfors
Keyword(s):  
Thyroid Hormone ◽  
Bone Age ◽  
Term Treatment ◽  
Point Of View ◽  
Chronological Age ◽  
Long Term Treatment ◽  
Thyroid Medication ◽  
Height Increase ◽  
Delayed Closure

ABSTRACT In 7 cases of dwarfism with markedly delayed closure of the epiphyses, methyltestosterone was administered sublingually in doses of 5–10 (25) mg daily in combination with thyroid hormone in doses of 25–120 mg daily for 2–7 years. At the institution of treatment the patients were 9, 11, 15, 15, 16, 17 and 20 years old and were 95, 125, 119, 124, 120, 135 and 125 cm in height respectively. The bone age was in all cases checked against Greulich & Pyle's radiographic tables (1950). During the first two years of therapy, 5 patients exhibited a more rapid increase of the bone age than was to be expected considering their chronological age. In 5 cases where the therapy was continued over a longer period of time, such a tendency was not demonstrable later, although the dosage of methyltestosterone was often somewhat increased. On the contrary, a retardation of the bone age development occurred, as compared with the chronological age. In none of the present cases have the epiphyses become closed, notwithstanding a considerable height increase in all cases, i. e. 15–29 cm depending on the length of the period of treatment, and the relatively advanced age of the patients at the time of writing when they are still under androgen therapy with or without thyroid medication. Provided that the bone age is continuously checked, it appears that methyltestosterone in small doses can safely be used in the treatment of dwarfism with delayed closure of the epiphyses. This trea[ill]ment proved to be of great importance from the point of view of the choice of a vocation as well as for the future life of the patients.

scholarly journals Long-Term Effect of Aromatase Inhibition in Aromatase Excess Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A679-A679
Author(s):  
Gerhard Binder ◽  
Akie Nakamura ◽  
Roland Schweizer ◽  
Tsutomu Ogata ◽  
Maki Fukami ◽  
...  
Keyword(s):  
Tandem Duplication ◽  
Low Dose ◽  
Adult Height ◽  
Bone Age ◽  
Sporadic Case ◽  
Term Treatment ◽  
Sibling Pairs ◽  
Long Term Effect ◽  
Long Term Treatment

Abstract Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. Long-term treatment effects of aromatase inhibitors are unknown. Retrospectively we collected data from file records of 7 boys (three sibling pairs and one sporadic case) with AEXS. Genetic analysis revealed upstream of CYP19A1 a 165,901 bp deletion in 4 German cousins, a 198,662 bp deletion in 2 Japanese brothers and a 387,622 bp tandem duplication in a Japanese boy. All boys developed prepubertal gynecomastia, at 9.0 yr of age (median; range: 7.0 - 11.0). Height was +1.20 SDS (-0.24 - +1.98); predicted adult height was -1.29 (-3.29 - +1.09 SDS). Four boys were treated with anastrozole 1.0 mg daily, while three reached adult height untreated. Treatment with anastrozole was stopped after 5.6 yr (4.0 - 6.8). Three treated boys exceeded height prognosis by 2.4, 6.9 and 8.1 cm; while one untreated fell below prognosis by 8.6 cm. One treated with a low dose and two untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 - -0.29) and -0.15 SDS without (-2.31 - -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 - +0.52) and +0.54 SDS without treatment (+0.23 - +1.30). Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by aromatase inhibitor anastrozole (1 mg daily) promotes adult height in boys with AEXS.

Long-term Effect of Aromatase Inhibition in Aromatase Excess Syndrome

2021 ◽  
Author(s):  
Gerhard Binder ◽  
Akie Nakamura ◽  
Roland Schweizer ◽  
Tsutomu Ogata ◽  
Maki Fukami ◽  
...  
Keyword(s):  
Tandem Duplication ◽  
Low Dose ◽  
Adult Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Term Treatment ◽  
Long Term Effect ◽  
Long Term Treatment ◽  
Age Range

Abstract Context Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. Objective The objective was to study long-term treatment effects of an aromatase inhibitor. Methods Data from 7 boys with AEXS were retrospectively collected. Genetic analysis revealed upstream of CYP19A1 a 165 901 bp deletion in 4 German cousins, a 198 662 bp deletion in 2 Japanese brothers, and a 387 622 bp tandem duplication in a Japanese boy. Results All boys developed prepubertal gynecomastia, at median 9.0 years of age (range: 7.0-11.0). Height was +1.20 standard deviation score (SDS) (–0.24 to +1.98); predicted adult height was -1.29 SDS (-3.29 to +1.09). Four boys were treated with 1.0 mg of anastrozole daily, while 3 reached adult height untreated. Treatment with anastrozole was stopped after 5.6 years (4.0-6.8). Three treated boys exceeded their prognosis by 2.4, 6.9, and 8.1 cm, while 1 untreated boy fell below the prognosis by 8.6 cm. One treated with a low dose and 2 untreated reached their prognosis. Adult heights were –0.91 SDS with anastrozole (–2.86 to –0.29) and –0.15 SDS without (–2.31 to –0.03). Distance to target height was –0.22 SDS with anastrozole (–1.72 to +0.52) and +0.54 SDS without (+0.23 to +1.30). Conclusion Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by anastrozole promotes adult height in boys with AEXS.

Double-blind, placebo-controlled, dose-response trial of oral clodronate in patients with bone metastases.

1995 ◽  
Vol 13 (4) ◽  
pp. 929-934 ◽  
Author(s):  
N O'Rourke ◽  
E McCloskey ◽  
F Houghton ◽  
H Huss ◽  
J A Kanis
Keyword(s):  
Term Treatment ◽  
Calcium Excretion ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Treatment Groups ◽  
Pain Scores ◽  
Long Term Treatment ◽  
Significant Difference ◽  
Oral Clodronate

PURPOSE Despite evidence that clodronate inhibits tumor-induced osteolysis, no studies have directly assessed the optimal dose for long-term treatment. The aim of this double-blind, placebo-controlled study was to determine the safety and efficacy of different doses of clodronate in affected patients. PATIENTS AND METHODS Eighty-four patients with tumor-induced osteolysis were randomized to receive treatment with placebo, or 400 mg, 1,600 mg, or 3,200 mg of clodronate, daily for 4 weeks. Patients were reviewed weekly during treatment. Fasting urinary calcium excretion was the primary variable used to assess response. Visual analog pain scores and adverse events were documented. RESULTS In the clodronate-treated groups, there was a dose-dependent reduction in fasting calcium excretion with a highly significant difference between placebo and 1,600 mg clodronate (P = .0002) and placebo and 3,200 mg clodronate (P = .0001), but no significant difference between 1,600 mg and 3,200 mg clodronate. There was no discernible change in pain scores or analgesic requirements. Bone-derived isoenzyme alkaline phosphatase values increased in all groups, with a significant difference between baseline and final values in the 1,600-mg and 3,200-mg groups (P < .01 and P = .03, respectively). Adverse events were distributed evenly across the four treatment groups. Compliance was greater than 99% in all treatment groups. CONCLUSION Oral clodronate at a dose of 1,600 mg or 3,200 mg will inhibit bone resorption. Since there was no significant difference between these two doses in terms of efficacy at 4 weeks, 1,600 mg/d can be recommended for long-term treatment. This dose is well tolerated and may promote bone repair, as judged by increases in bone alkaline phosphatase levels.

scholarly journals Inhibition of FGFR Signaling Partially Rescues Hypophosphatemic Rickets in HMWFGF2 Tg Male Mice

Endocrinology ◽  
2017 ◽  
Vol 158 (10) ◽  
pp. 3629-3646 ◽  
Author(s):  
Liping Xiao ◽  
Erxia Du ◽  
Collin Homer-Bouthiette ◽  
Marja M Hurley
Keyword(s):  
Cortical Bone ◽  
Bone Mineral ◽  
Term Treatment ◽  
Hypophosphatemic Rickets ◽  
Fgf Receptor ◽  
Tissue Density ◽  
Long Term Treatment ◽  
Fgfr Signaling ◽  
Total Body

Abstract Transgenic mice harboring high molecular weight fibroblast growth factor (FGF)2 isoforms (HMWTg) in osteoblast lineage cells phenocopy human X-linked hypophosphatemic rickets (XLH) and Hyp murine model of XLH demonstrating increased FGF23/FGF receptor signaling and hypophosphatemic rickets. Because HMWFGF2 was upregulated in bones of Hyp mice and abnormal FGF receptor (FGFR) signaling is important in XLH, HMWTg mice were used to examine the effect of the FGFR inhibitor NVP-BGJ398, now in clinical trials for cancer therapy, on hypophosphatemic rickets. Short-term treatment with NVP-BGJ398 rescued abnormal FGFR signaling and hypophosphatemia in HMWTg. Long-term treatment with NVP-BGJ398 normalized tail, tibia, and femur length. Four weeks NVP-BGJ398 treatment significantly increased total body bone mineral density (BMD) and bone mineral content (BMC) in HMWTg mice; however, at 8 weeks, total body BMD and BMC was indistinguishable among groups. Micro-computed tomography revealed decreased vertebral bone volume, trabecular number, and increased trabecular spacing, whereas femur trabecular tissue density was increased; however, NVP-BGJ398 rescued defective cortical bone mineralization, increased thickness, reduced porosity, and increased endosteal perimeter and cortical tissue density in HMWTg. NVP-BGJ398 improved femur cancellous bone, cortical bone structure, growth plate, and double labeling in cortical bone and also increased femur trabeculae double labeled surface, mineral apposition rate, bone formation rate, and osteoclast number and surface in HMWTg. The decreased NPT2a protein that is important for renal phosphate excretion was rescued by NVP-BGJ398 treatment. We conclude that NVP-BGJ398 partially rescued hypophosphatemic rickets in HMWTg. However, long-term treatment with NVP-BGJ398 further increased serum FGF23 that could exacerbate the mineralization defect.

SERUM LEVELS OF SOMATOMEDIN A AND GROWTH DURING LONG-TERM TREATMENT OF PATIENTS WITH PITUITARY DWARFISM WITH HUMAN GROWTH HORMONE

1979 ◽  
Vol 92 (3) ◽  
pp. 385-397 ◽  
Author(s):  
Kazue Takano ◽  
Naomi Hizuka ◽  
Kazuo Shizume ◽  
Yoko Hasumi
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Bone Age ◽  
Serum Levels ◽  
Term Treatment ◽  
Duration Of Treatment ◽  
Pituitary Dwarfism ◽  
Long Term Treatment

ABSTRACT Eighteen patients with pituitary dwarfism were treated for 1 7/12 to 6 years with human growth hormone (hGH) at a dose of 0.19–0.62 unit (U) per kg of body weight per week. The mean increment in height was 2.0 ± 0.4 and 8.8 ± 0.5 cm/year before and the first year after treatment of hGH, respectively. A significant positive correlation was observed between serum levels of somatomedin A and growth rate, especially in children with bone age below 10 and a duration of treatment of less than one year (r = 0.66, P < 0.005). Long-term treatment with hGH was accompanied by a decreasing response. However, the serum levels of somatomedin A did not decrease significantly. Therefore, decreased growth increment in these situations was not due to decreased serum levels of somatomedin A.

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