Because of the short duration of GH treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. Interestingly, GH treatment to GHD adults initially results in increased bone resorption with an increased number of bone-remodeling units and more newly produced unmineralized bone, resulting in an apparent low or unchanged bone mass.
However, GH treatment for more than 18 months gives increased bone formation and bone mineralization of newly produced bone and a concomitant increase in bone mass as determined with DEXA. Thus, the action of GH on bone metabolism in GHD adults is 2-fold: it stimulates both bone resorption and bone formation. We therefore propose "the biphasic model" of GH action in bone remodeling Fig.
According to this model, GH initially increases bone resorption with a concomitant bone loss that is followed by a phase of increased bone formation. After the moment when bone formation is stimulated more than bone resorption transition point , bone mass is increased. However, a net gain of bone mass caused by GH may take some time as the initial decrease in bone mass must first be replaced Fig. When all clinical studies of GH treatment of GHD adults are taken into account, it appears that the "transition point" occurs after approximately 6 months and that a net increase of bone mass will be seen after months of GH treatment.
During week treatment, the daily rhGH dose was started from subcutaneous injection of 1. All patients were followed at our GHD clinic. At the start of the study and every eight weeks, physical and laboratory examinations were performed. Anthropometric parameters including height, weight, waist circumference, and hip circumference were measured with standard protocols in early morning with light clothes.
BMI was calculated as weight kg divided by height m squared. FFM index and FM index were calculated as described previously [ 17 ]. Informed consent was obtained from all patients. All data were de-identified before analysis.
Blood samples were obtained in the morning after an overnight fasting. Briefly, when a scout scan was finished, reference lines were placed at the distal end plates for both the radius and tibia. Each scan was comprised of slices, corresponding to a Scans were graded for motion artifacts as described previously [ 19 ]. Bone microarchitecture parameters were obtained with the standard morphologic analysis by semiautomated software, including trabecular area Tb. Ar , cortical area Ct.
Ar , cortical perimeter Ct. Pm , total volume bone mineral density Tt. Sp , in-homogeneity of network Tb. SD , cortical thickness Ct. Th , and cortical porosity Ct. Non-normal data are presented as median and ranges, and Wilcoxon signed-rank test was used for data analysis.
All of the statistical computations were run using SPSS software version A total of 9 male patients with CO AGHD with a mean age of 28 years range, 21—51 were enrolled in this prospective study.
Five patients had pituitary stalk interruption, and four patients had pituitary hypoplasia based on MRI. Eight patients stopped rhGH replacement after completion of linear growth. Duration of rhGH replacement treatment was The average time course since the cessation of rhGH treatment was 7. One patient never accepted rhGH treatment before, and he was 51 years old at the time of the start of this study.
All patients had multiple pituitary hormone deficiency and sustained glucocorticoid and levothyroxine replacement since childhood.
All patients had no signs of diabetes insipidus. No clinical fracture was reported from all our patients. After 24 weeks of treatment, there was a 0. No significant changes were found in waist-hip ratio. Fat mass percentage decreased from Fat mass index decreased from 7. No significant changes were found in fat-free mass index. Grip strength of nondominant hand had not been improved at the end of study Table 1.
Endocrinological and biochemical parameters are listed in Table 2. With constant replacement of levothyroxine, FT3 was stable during the study and FT4 levels decreased from 1. No routine calcium or vitamin D supplementation was prescribed during the study. Serum calcium levels remained stable after 24 weeks treatment.
There were significant increases in serum phosphate 1. Serum 25OHD decreased from There was no difference in other biochemical parameters including fasting glucose, hemoglobulin, ALT, AST, albumin and uric acid at baseline and after 24 weeks of treatment. There was significant decrease in trabecular area No significant changes were found in cortical vBMD, cortical perimeter, and intracortical porosity of the distal tibia.
No significant changes were found in trabecular vBMD, trabecular thickness, and trabecular number or trabecular separation after 24 weeks of rhGH treatment. The detailed changes of some important HR-pQCT parameters of the distal tibia at baseline and after 24 weeks of rhGH treatment are presented in Figure 1.
After week rhGH replacement therapy, there were significant improvements of cortical perimeter There was a significant decrease in trabecular number 1. No significant changes were found in total vBMD, cortical area, cortical thickness, and trabecular vBMD or trabecular area after 24 weeks of rhGH treatment. The detailed changes of some important HR-pQCT parameters of the distal radius at baseline and after 24 weeks of rhGH treatment are presented in Figure 2.
In our previous work, we found that adult male patients with CO AGHD who are no longer receiving GH replacement have abnormalities in bone microarchitecture and estimated bone strength [ 14 ]. Our results showed that rhGH significantly improved vBMD in distal tibia and bone microarchitecture in both distal tibia and radius, accompanied by increased bone resorption biomarkers in a very early stage of treatment. GH and IGF-1 act in an endocrine, paracrine, or autocrine fashion to regulate osteoblast, osteocyte, and osteoclast function and thus sustains normal cortical and trabecular bone properties [ 21 , 22 ].
Kinetic studies demonstrated that bone calcium deposition reaches a maximum during puberty, which is approximately five times that of adulthood [ 23 ]. Bone microarchitecture was reported to be marginally reduced [ 24 ] or not changed [ 13 ] in some AGHD patients.
There were also some studies which reported that short-term rhGH treatment increased bone turnover but did not increase BMC [ 26 ]. Evaluation of BMD and BMC in all these studies is based on DXA, which does not provide details of microarchitecture of cortical and cancellous bones and could not detect subtle changes of bone in early stages of rhGH treatment.
Our data found that rhGH is beneficial for cortical bone, including increased cortical area, cortical perimeter, and cortical thickness. These data suggested that rhGH could promote subperiosteal bone formation. At the same time, the reduction of cancellous bone area suggested cortification of cancellous bone after rhGH treatment, which is significant for maintaining the mechanical stability of bone and increasing the antifracture ability of long bone after rhGH treatment.
The baseline serum vitamin D level was insufficient in our patients, and vitamin D was not supplemented during this short-term pilot study in order to avoid confounding variables to evaluate the effect of rhGH on bone volumetric density and microstructure.
Further studies are required to assess the add-on effect of vitamin D in these patients. The main limitation of this study is the small number of participants.
Another limitation is that there could be a selection bias in the study. Eight of the nine patients in the study undertook treatment with rhGH during childhood while the older one 51 years never undertook treatment before enrollment. We enrolled this patient since this is a self-controlled prospective study. Another limitation is the relatively short term of treatment in our patients.
Bone mass increases steadily through childhood, peaking in the mid 20s. Subsequently, there is a slow decline that accelerates in late life. During childhood, the accumulation in bone mass is a combination of bone growth and bone remodeling. Bone remodeling is the process of new bone formation by osteoblasts and bone resorption by osteoclasts. GH directly and through IGF-I stimulates osteoblast proliferation and activity, promoting bone formation.
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