Annals of Nephrology

ISSN: 2642-4827

RESEARCH ARTICLE | VOLUME 1 | ISSUE 1 OPEN ACCESS

The Prevalence of Vitamin D Deficiency and Secondary Hyperparathyroidism in Elderly Male Patients with Hip Fracture: Time for Vitamin D and Testosterone Replacement

Awad Magbri, Gussail, Eussera El-Magbri, Smew, Mariam El-Magbri, Taha El-Magbri, H Grimes and J Kelly

  • Awad Magbri 1*
  • Gussail 1
  • Eussera El-Magbri 1
  • Smew 1
  • Mariam El-Magbri 1
  • Taha El-Magbri 1
  • H Grimes 1
  • J Kelly 1
  • Departments of Medicine, Orthopedics, Public Health Promotion and Laboratory Medicine, University College Hospital Galway, Ireland

Magbri A, Gussail, El-Magbri E, et al. (2016) The Prevalence of Vitamin D Deficiency and Secondary Hyperparathyroidism in Elderly Male Patients with Hip Fracture: Time for Vitamin D and Testosterone Replacement. Ann Nephrol 1(1):1-4.

Accepted: September 30, 2016 | Published Online: October 03, 2016

The Prevalence of Vitamin D Deficiency and Secondary Hyperparathyroidism in Elderly Male Patients with Hip Fracture: Time for Vitamin D and Testosterone Replacement

Abstract


Twenty eight male patients with non-pathological fracture neck of femur (FNOF), age range 61-89 years, mean age 74.4 years, presented for surgery for fracture neck of femur to Merlin Park Regional Hospital, Galway Ireland and 28 age and sex matched control patients, age range 60-85 years, mean age 72.4 years who were admitted to the medical ward for various complaints including chest pain, gastroenteritis, and upper respiratory tract infections were included in the study. Following a formal written consent blood were collected for CBC, CMP, and total and free testosterone levels, LH, Estradiol, total 25(OH)D and 1,25(OH)2D, and PTH levels pre-operatively. Bone mineral density was done within 7 days of the incident fracture on the patients and the control groups after enrollment. The study is approved by the local IRB.

The results were analyzed using T-test for paired data and Chi-square test for the dichotomous data when applicable. The levels of free and total testosterone (< 0.001), LH (< 0.001), total protein (< 0.001), albumin (< 0.001), PTH (< 0.001), and free estradiol levels (< 0.04) were significantly low in patients with hip fracture compared to controls. The BMD of the femoral neck in g/cm2 were also significantly lower in the patient compared to controls (P < 0.001).

Conclusions

Vitamin D and testosterone deficiency are potentially preventable risk factors in elderly male patients with non-pathological hip fracture. Vitamin D deficiency might also be implicated for the rise in PTH levels, secondary hyperparathyroidism and bone mineral disorders. Hormonal treatment may be potential option to prevent osteoporosis and decrease the risk of hip fracture in elderly male patients.

Keywords


Osteoporosis, Fracture neck of femur, Hip fracture, Testosterone, Bone mineral density, Vitamin D, 25(OH)D, 1, 25(OH)2D, Secondary hyperparathyroidism

Introduction


Vitamin D and hormonal deficiency are well recognized disorders in elderly women. However, there has been insufficient awareness in the medical profession or the public arena that these disorders are leading secondary causes for osteoporosis in elderly males [1-5]. Osteoporotic fractures are public health problems and any measures to curtail their frequency will have a great impact on the health delivery and expenditure. Minimal trauma in the form of falls, reduced bone density, and impaired bone quality all contribute to fracture risks [6-9]. The incidence of hip fracture increases sharply after 75 years of age in both male and female patients. There is encouraging data from Canada and elsewhere that the age-standard rate decline in hip fracture in both females and males is occurring [10-12]. However, the one year mortality and the need for institutional care after hip fracture are higher in men than women [13-16]. On the other hand, men are less likely to be investigated and treated for secondary causes of osteoporosis excluding age [14]. How common is osteoporosis in men? Has not unfortunately, been answered clearly and sufficiently as the case in women. Even though, the definition of osteoporosis in men is ambiguous (-2.5 T-score below the normal young males), It is estimated that 3-6% of males > 50 years of age are osteoporotic, compared to 22% in women [15]. Between 28-60% of fractures in elderly females > 80 yrs are attributed to osteoporosis [15,16]. Bone quantity and quality as well as the extent of trauma are important determinants of hip fracture in this age group [17-19].

Even though that androgen deficiency and advanced age have been associated with increased parathyroid hormone (PTH) level [20,21]. Reduced levels of 25-hydroxycholecalciferol [25(OH)D] and 1,25-dihydroxycholecalciferol [1,25(OH)2D] [22-25] may have contributed to the frequent occurrence of hip fracture in elderly male patients. This study intended to investigate the factors contributing to hip fractures in elderly male patients. By shedding light on the dominant factors influencing hip fracture in male patients it is hoped that preventive measures would be implemented to curb this epidemics.

Participants and Methods


This study included 28 elderly male patients with fracture neck of femur who were admitted to the orthopedic ward for surgery. The age range of these patients was 61-89 years, mean age 74.4 years. A 28 age and sex matched elderly male patients (age range 60-85 years, mean age 72.4 years) admitted to the medical ward for various medical problems, including chest pain, gastroenteritis, or upper respiratory tract infection were included. Informed consent was obtained from each participant in the study and the study is approved by the local IRB. The 2 groups are well balanced for age, weight and height, activity of daily livings, tobacco and alcohol consumption.

The eligibility criteria are age > 60 years, participants should have no previous fracture, no use of steroids or vitamin D supplements. Patients had to be ambulatory and have suffered a fracture neck of femur due to minor trauma (fall). All blood samples were taken from the patients within 24 hours to minimize the effect of trauma on the biochemical parameters. The exclusion criteria include: i) pathological fracture ii) Previous fracture or fractures of femurs secondary to trauma other than falls iii) Thyroid diseases iv) Alcohol abuse v) Use of calcium or vitamin D supplements vi) Use of thiazide, bisphosphonate, calcitonin or corticosteroids medications for more than 3 months.

Blood was drawn from each participant including the control group for estimations of parathyroid hormone (PTH), vitamin D levels, CBC, complete metabolic panel, luteinizing hormone (LH), testosterone, and estradiol levels. Bone mineral density scan of the proximal femur and femoral neck were done within one week from the patients and controls using dual-energy X-ray absorptiometry (DXA). Area bone mineral density (BMD) was used measured using Lunar DPX-L scanner (Lunar Corp., Madison, WI, USA) according to the manufacture specification.

Statistical analysis

All statistical analysis was done using the SAS (Statistical analysis systems Inc. NC, USA). P value of 0.05 or less is taken as significant results. Student T-test is used for continuous data and all P value is reported as two-sided. Dichotomous data are analyzed using the chi-square test whenever applicable.

Results


Serum vitamin D levels below the reference range were found in 19/28 (68%) of patients with hip fracture compared to 3/28 (10.7%) in control subjects. Both 25(OH)D 23/28 (82%) vs. 4/28 (14.3%) and 1,25(OH)2D levels were significantly lower in patients compared to controls. This may explain the significant higher levels of PTH and evidence of compensatory secondary hyperparathyroidism in patients compared to control subjects. The PTH levels were higher in patients compared to control 16/28 (57.1%) vs. 2/28 (7.1%).

Total protein and albumin levels were significantly lower in patients compared to control subjects. The trauma incurred during fall with fractures could have been contributing factors to low levels of proteins and albumin in patients compared to control subjects. Calcium, phosphorus, and creatinine levels are similar in the 2 groups. No significant difference observed between the 2 groups as far as age, height, tobacco habits, and alcohol consumption. However, the BMI was significantly lower in patients compared to control subjects table 1.

Serum total and free testosterone levels less than the reference value (280-1070 ng/dl) were found in 24/28 (85.7%) and 26/28 (92.9%) of patients compared to 5/28 (17.9%) and 3/28 (10.7%) in controls, respectively. As a results of low androgen levels secondary to primary gonad insufficiency the LH is significantly higher in patients compared to controls.

Bone mineral density at the proximal femoral and femoral neck were lower in patients compared to controls, denoting evidence of osteoporosis probably secondary to testosterone and vitamin D deficiencies in patients compared to controls table 1.

Discussion


Low vitamin D with secondary hyperparathyroidism (SHPT) and decreased radial bone density in elderly men was illustrated in Baltimore Longitudinal Study of Aging and others [26,27]. In a study involving 133 community based elderly men the inverse relationship between high level of PTH after adjusting for BMI and low level of BMD of multiple femoral sites have supporting the notion that SHPT may contribute to bone loss in elderly men with increased incidence of hip fracture. The high levels of PTH coupled with low levels of 25(OH)D in patients with hip fracture is in agreement with this study [28-30]. Even after adjusting for protein binding, the low levels of 25(OH)D in patients with hip fracture is well demonstrated. These findings are concurring with our results [30]. The compensatory increase in the levels of 1,25(OH)2D in patients denoting that the activity of 1 α-hydroxylase enzyme is sensitive to PTH levels even in elderly men [31]. The normal levels of 1,25(OH)D in patients with hip fracture may explain the low incidence of osteomalacia in cases of hip fracture [32,33]. Moreover, the increased activity of 1α-hydroxylase brings about normalization of 1,25(OH)D at the expense of low levels of 25(OH)D3. This effect is mediated by high levels of PTH.

The androgen deficiencies in hip fracture patients along with high levels of LH are consistent with primary gonadal failure [34]. Androgens are indeed essential for the maintenance of bone mass; especially if we believe that hypogonadism in adult men is associated with osteopenia [35-37]. In this study androgen levels were significantly lower in patients than controls; however, estradiol value did not. Androgen has both direct and indirect effect on bone metabolism. On the other hand, androgen is transformed into estrogen through the intermediary activities of aromatase enzymes. This might explain the normal levels of estradiol in these patients [38]. There have been reports that treatment with testosterone in hypogonadal adults could result in high BMD with reversal of bone loss [39,40]. Androgen and vitamin D deficiencies in elderly men with hip fracture have additive but not synergistic effect.

This study and others have shed light on how common androgen and vitamin D deficiencies in elderly male patients with osteoporotic hip fractures. This study also showed that (68% and 92.9%) of elderly male patients with hip fracture had vitamin D and testosterone deficiencies, respectively, while 57.1% had increased levels of PTH as a compensatory SHPT from low 25(OH)D levels. These staggering numbers call for further studies to evaluate the importance of vitamin D and testosterone supplementation to prevent osteoporotic hip fractures in this section of population.

The limitation of this study is that markers of bone resorption were not done. The small sample size and effects of other cofounders like trauma on the levels of protein, albumin, and testosterone in these patients could not be entirely dismissed. A cross-sectional study like this can not suggest cause and effect relationships between androgen and vitamin D and bone resorption. Our study also was not design to study the effects of hormone replacement therapy on the quality and quantities of underlying bone fracture.

Conclusion


Vitamin D and testosterone deficiency are potentially preventable risk factors in elderly male patients with non-pathological hip fracture. Vitamin D deficiency might also be implicated for the rise in PTH levels, secondary hyperparathyroidism and bone mineral disorders. Hormonal treatment may be potential option to prevent osteoporosis and decrease the risk of hip fracture in elderly male patients.

The authors have nothing to disclose.

References


  1. Rudman D, Drinka PJ, Wilson CR, et al. (1994) Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men. Clin Endocrinol (Oxf) 40: 653-661.
  2. Murphy S, Khaw KT, Cassidy A, et al. (1993) Sex hormones and bone mineral density in elderly men. Bone Miner 20: 133-140.
  3. Greendale GA, Edelstein S, Barrett-Connor E (1997) Endocrine sex steroids and bone mineral density in older women and men: The Rancho Bernardo study. J Bone Miner Res 12: 1833-1843.
  4. Smith EP, Boyd J, Frank GR, et al. (1994) Estrogen resistance caused by a mutation in the estrogen- receptor gene in a man. N Engl J Med 331: 1056-1061.
  5. Khosla S, Melton LJ, Atkinson EJ, et al. (1994) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bio-available estrogen. J Clin Endocrinol Metab 83: 2266-2274.
  6. Brunner LC, Oates LE (2003) Hip fractures in adults. Am Fam Physician 67: 537-543.
  7. Parker M, Johansen A (2006) Hip fracture. BMJ 333: 27-30.
  8. Gillespie WJ (2001) Hip fracture. BMJ 321: 968-975.
  9. Bookvar KS, Halm EA, Litke A, et al. (2003) Hospital readmissions after hospital discharge for hip fractures: Surgical and non-surgical causes and effects outcomes. J Am Geriatr Soc 51: 399-403.
  10. Cummings SR, Melton IJ (2002) Epidemiology and outcomes of osteoporosis fractures. Lancet 359: 1761-1767.
  11. Beer C, Giles E (2005) Hip fracture--challenges in prevention and management. Aus Fam Physician 34: 673-676.
  12. Paksima N, Kenneth JK, Aharanoff G, et al. (2008) Predictors of mortality after hip fracture: a 10-year prospective study. Bull NYU Hosp Je Dis 66: 111-117.
  13. Leslie WD, O’Donnell S, Jean S, et al. (2009) Trends in hip fracture rates in Canada. JAMA 302: 883-889.
  14. Papaioannou A, Kennedy CC, Loannidis G et al. (2008) The osteoporosis care gap in men with fragility fracture: The Canadian Multicenter Osteoporosis Study. Osteoporosis Int 19: 581-587.
  15. Schuit SC, van der Klift M, Weel AE, et al. (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34: 195-202.
  16. Stone KL, Seeley DG, Lui LY, et al. (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the study of Osteoporotic Fractures. J Bone Miner Res 18: 1947-1954.
  17. Zebaze RM, Ghasem-Zadel A, Bohte A, et al. (2010) Intracortical remodeling and porosity in the distal radius and postmortem femurs of women: A cross-sectional study. Lancet 375: 1729-1736.
  18. Khosla S, Riggs BL, Atkinson EJ, et al. (2006) Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res 21: 124-131.
  19. Orwoll E, Marshall LM, Nielson CM, et al. (2008) Finite element analysis of the proximal femur and hip fracture risk in older men. J Bone Miner Res 24: 475-483.
  20. Young G, Marcus R, Mioff JR, et al. (1987) Age-related rise in parathyroid hormone in man: the use of intact and mid-molecule antisera to distinguish hormone secretion from retention. J Bone Miner Res 2: 367-374.
  21. Endres DB, Morgan CH, Garry PJ, et al. (1987) Age-related changes in serum immunoreactive parathyroid hormone and its biological action in healthy men and women. J Clin Endocrinol Metab 65: 724-731.
  22. Orwoll ES, Meier DE (1986) Alteration in calcium, vitamin D, and pathyroid hormone physiology in normal men with ageing: Relationship to the development of senile osteopenia. J Clin Endocrinol 63: 1262-1269.
  23. Epstein S, Bryce G, Hinman JW, et al. (1986) The influence of age on bone mineral regulating hormones. Bone 7: 421-425.
  24. Halloran BP, Portale AA, Lonergan ET, et al. (2009) Production and metabolic clearance of 1,25-dihydroxyvitamin D in men: Effect of advancing age. J Clin Endocrinol 70: 318-323.
  25. Chapuy M, Arlot M, Duboeuf F, et al. (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327: 1637-1642.
  26. Riggs BL, Melton LJ (1986) Involutional osteoporosis. N Engl J Med 314: 1676-1686.
  27. Sherman SS, Tobin JD, Hollis BW, et al. (1992) Biochemical parameters associated with low bone density in healthy men and women. J Bone Miner Res 7: 1123-1130.
  28. Pun K, Wong F, Wang C, et al. (1990) Vitamin D status among patients with fractured neck of femur in Hong-Kong. Bone 11: 365-368.
  29. MacDonald D, Lan E, Chan E, et al. (1992) Serum intact parathyroid hormone level in elderly Chinese females with hip fracture. Calcif Tissue Int 51: 412-414.
  30. Benhamou C, Tourliere D, Gauvain J, et al. (1995) Calciotopic hormones in elderly people with and without hip fracture. Osteoporos Int 5: 103-107.
  31. Bouillon R, Auwerx J, Lissens W, et al. (1987) Vitamin D status in the elderly: Seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency. Am J Clin Nutr 45: 755-763.
  32. Lips P, Netelenbos J, Jongen M, et al. (1982) Histomorphometric profile and vitamin D status in patients with femoral neck fracture. Metab Bone Dis Rel Res 4: 85-93.
  33. Compston J, Vedi S, Croucher P (1991) Low prevalence of osteomalacia in elderly patients with hip fracture. Age Ageing 20: 132-134.
  34. Selby C (1990) Sex hormone binding globulin: origin, function and clinical significance. Ann Clin Biochem 27: 532-541.
  35. Orwoll ES, Klein RF (1995) Osteoporosis in men. Endocr Rev 16: 87-116.
  36. Finkelstein JS, Klibanski A, Neer RM, et al. (1987) Osteoporosis in men with idiopathic hypogonadotrophic hypogonadism. Ann Intern Med 106: 354-361.
  37. Greenspan SL, Oppenheim DS, Klibanski A (1989) Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. Ann Intern med 110: 526-531.
  38. Van den Beld AW, Frank H, De Jong, et al. (2000) Measures of bioavailabel serum Testosterone and Estradiol and Their Relationships with Muscle Strengh, Bone Density, and Body Composition in Elderly Men. J Clin Endocrionol Metabol 85: 3276-3282.
  39. Isaia G, Mussetta M, Pecchio, et al. (1992) Effects of testosterone on bone in hypogonadal males. Maturitas 15: 47-51.
  40. Devogelaer J, De Cooman S, Nagant De Deuxchaisnes C (1992) Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. Maturitas 15: 17-23.

Abstract


Twenty eight male patients with non-pathological fracture neck of femur (FNOF), age range 61-89 years, mean age 74.4 years, presented for surgery for fracture neck of femur to Merlin Park Regional Hospital, Galway Ireland and 28 age and sex matched control patients, age range 60-85 years, mean age 72.4 years who were admitted to the medical ward for various complaints including chest pain, gastroenteritis, and upper respiratory tract infections were included in the study. Following a formal written consent blood were collected for CBC, CMP, and total and free testosterone levels, LH, Estradiol, total 25(OH)D and 1,25(OH)2D, and PTH levels pre-operatively. Bone mineral density was done within 7 days of the incident fracture on the patients and the control groups after enrollment. The study is approved by the local IRB.

The results were analyzed using T-test for paired data and Chi-square test for the dichotomous data when applicable. The levels of free and total testosterone (< 0.001), LH (< 0.001), total protein (< 0.001), albumin (< 0.001), PTH (< 0.001), and free estradiol levels (< 0.04) were significantly low in patients with hip fracture compared to controls. The BMD of the femoral neck in g/cm2 were also significantly lower in the patient compared to controls (P < 0.001).

Conclusions

Vitamin D and testosterone deficiency are potentially preventable risk factors in elderly male patients with non-pathological hip fracture. Vitamin D deficiency might also be implicated for the rise in PTH levels, secondary hyperparathyroidism and bone mineral disorders. Hormonal treatment may be potential option to prevent osteoporosis and decrease the risk of hip fracture in elderly male patients.

References

  1. Rudman D, Drinka PJ, Wilson CR, et al. (1994) Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men. Clin Endocrinol (Oxf) 40: 653-661.
  2. Murphy S, Khaw KT, Cassidy A, et al. (1993) Sex hormones and bone mineral density in elderly men. Bone Miner 20: 133-140.
  3. Greendale GA, Edelstein S, Barrett-Connor E (1997) Endocrine sex steroids and bone mineral density in older women and men: The Rancho Bernardo study. J Bone Miner Res 12: 1833-1843.
  4. Smith EP, Boyd J, Frank GR, et al. (1994) Estrogen resistance caused by a mutation in the estrogen- receptor gene in a man. N Engl J Med 331: 1056-1061.
  5. Khosla S, Melton LJ, Atkinson EJ, et al. (1994) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bio-available estrogen. J Clin Endocrinol Metab 83: 2266-2274.
  6. Brunner LC, Oates LE (2003) Hip fractures in adults. Am Fam Physician 67: 537-543.
  7. Parker M, Johansen A (2006) Hip fracture. BMJ 333: 27-30.
  8. Gillespie WJ (2001) Hip fracture. BMJ 321: 968-975.
  9. Bookvar KS, Halm EA, Litke A, et al. (2003) Hospital readmissions after hospital discharge for hip fractures: Surgical and non-surgical causes and effects outcomes. J Am Geriatr Soc 51: 399-403.
  10. Cummings SR, Melton IJ (2002) Epidemiology and outcomes of osteoporosis fractures. Lancet 359: 1761-1767.
  11. Beer C, Giles E (2005) Hip fracture--challenges in prevention and management. Aus Fam Physician 34: 673-676.
  12. Paksima N, Kenneth JK, Aharanoff G, et al. (2008) Predictors of mortality after hip fracture: a 10-year prospective study. Bull NYU Hosp Je Dis 66: 111-117.
  13. Leslie WD, O’Donnell S, Jean S, et al. (2009) Trends in hip fracture rates in Canada. JAMA 302: 883-889.
  14. Papaioannou A, Kennedy CC, Loannidis G et al. (2008) The osteoporosis care gap in men with fragility fracture: The Canadian Multicenter Osteoporosis Study. Osteoporosis Int 19: 581-587.
  15. Schuit SC, van der Klift M, Weel AE, et al. (2004) Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. Bone 34: 195-202.
  16. Stone KL, Seeley DG, Lui LY, et al. (2003) BMD at multiple sites and risk of fracture of multiple types: long-term results from the study of Osteoporotic Fractures. J Bone Miner Res 18: 1947-1954.
  17. Zebaze RM, Ghasem-Zadel A, Bohte A, et al. (2010) Intracortical remodeling and porosity in the distal radius and postmortem femurs of women: A cross-sectional study. Lancet 375: 1729-1736.
  18. Khosla S, Riggs BL, Atkinson EJ, et al. (2006) Effects of sex and age on bone microstructure at the ultradistal radius: a population-based noninvasive in vivo assessment. J Bone Miner Res 21: 124-131.
  19. Orwoll E, Marshall LM, Nielson CM, et al. (2008) Finite element analysis of the proximal femur and hip fracture risk in older men. J Bone Miner Res 24: 475-483.
  20. Young G, Marcus R, Mioff JR, et al. (1987) Age-related rise in parathyroid hormone in man: the use of intact and mid-molecule antisera to distinguish hormone secretion from retention. J Bone Miner Res 2: 367-374.
  21. Endres DB, Morgan CH, Garry PJ, et al. (1987) Age-related changes in serum immunoreactive parathyroid hormone and its biological action in healthy men and women. J Clin Endocrinol Metab 65: 724-731.
  22. Orwoll ES, Meier DE (1986) Alteration in calcium, vitamin D, and pathyroid hormone physiology in normal men with ageing: Relationship to the development of senile osteopenia. J Clin Endocrinol 63: 1262-1269.
  23. Epstein S, Bryce G, Hinman JW, et al. (1986) The influence of age on bone mineral regulating hormones. Bone 7: 421-425.
  24. Halloran BP, Portale AA, Lonergan ET, et al. (2009) Production and metabolic clearance of 1,25-dihydroxyvitamin D in men: Effect of advancing age. J Clin Endocrinol 70: 318-323.
  25. Chapuy M, Arlot M, Duboeuf F, et al. (1992) Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 327: 1637-1642.
  26. Riggs BL, Melton LJ (1986) Involutional osteoporosis. N Engl J Med 314: 1676-1686.
  27. Sherman SS, Tobin JD, Hollis BW, et al. (1992) Biochemical parameters associated with low bone density in healthy men and women. J Bone Miner Res 7: 1123-1130.
  28. Pun K, Wong F, Wang C, et al. (1990) Vitamin D status among patients with fractured neck of femur in Hong-Kong. Bone 11: 365-368.
  29. MacDonald D, Lan E, Chan E, et al. (1992) Serum intact parathyroid hormone level in elderly Chinese females with hip fracture. Calcif Tissue Int 51: 412-414.
  30. Benhamou C, Tourliere D, Gauvain J, et al. (1995) Calciotopic hormones in elderly people with and without hip fracture. Osteoporos Int 5: 103-107.
  31. Bouillon R, Auwerx J, Lissens W, et al. (1987) Vitamin D status in the elderly: Seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency. Am J Clin Nutr 45: 755-763.
  32. Lips P, Netelenbos J, Jongen M, et al. (1982) Histomorphometric profile and vitamin D status in patients with femoral neck fracture. Metab Bone Dis Rel Res 4: 85-93.
  33. Compston J, Vedi S, Croucher P (1991) Low prevalence of osteomalacia in elderly patients with hip fracture. Age Ageing 20: 132-134.
  34. Selby C (1990) Sex hormone binding globulin: origin, function and clinical significance. Ann Clin Biochem 27: 532-541.
  35. Orwoll ES, Klein RF (1995) Osteoporosis in men. Endocr Rev 16: 87-116.
  36. Finkelstein JS, Klibanski A, Neer RM, et al. (1987) Osteoporosis in men with idiopathic hypogonadotrophic hypogonadism. Ann Intern Med 106: 354-361.
  37. Greenspan SL, Oppenheim DS, Klibanski A (1989) Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. Ann Intern med 110: 526-531.
  38. Van den Beld AW, Frank H, De Jong, et al. (2000) Measures of bioavailabel serum Testosterone and Estradiol and Their Relationships with Muscle Strengh, Bone Density, and Body Composition in Elderly Men. J Clin Endocrionol Metabol 85: 3276-3282.
  39. Isaia G, Mussetta M, Pecchio, et al. (1992) Effects of testosterone on bone in hypogonadal males. Maturitas 15: 47-51.
  40. Devogelaer J, De Cooman S, Nagant De Deuxchaisnes C (1992) Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. Maturitas 15: 17-23.