Long Term Outcome of Bisphosphonate Therapy in Patients with Primary Hyperparathyroidism


Context: Primary hyperparathyroidism (PHPT) is commonly associated with reduced bone mineral density (BMD) presenting with osteoporosis, increasing the risk of bone fragility fractures in these patients. Bisphosphonates, due to their anti-resorptive action, are known to improve the BMD and reduce the risk of bone fragility fractures. Therefore, bisphosphonates are considered as an alternative to surgical treatment in managing osteoporosis in PHPT patients. Aim: The aim of this observational study was to assess the effect of long term bisphosphonate therapy on BMD, bone fragility fracture and biochemical markers of bone metabolism in patients with PHPT. Methodology: Fifty patients (mean age 74 years) with PHPT who were treated with long term bisphosphonate therapy were studied retrospectively. The mean baseline (before commencing bisphosphonate therapy) BMD T-scores for lumbar spine (L2-L4) and left femoral neck were -2.5 and -2.1, respectively. Fourteen patients had bone fragility fractures before initiation of bisphosphonate therapy. Results: After an average of 5 years of bisphosphonate treatment, there was a significant increase in lumbar BMD T-score (-2.5 to -2.1, p = 0.013) and a non-significant change in left femoral neck BMD T-score (-2.1 to -2.2, p = 0.497). There was no increase in bone fragility fracture rate (p = 0.167). Serum corrected calcium reduced from 2.74 mmol/L to 2.60 mmol/L (p < 0.001) and urine calcium to creatinine ratio from 0.70 to 0.55 (p < 0.0001), both within the reference range. Conclusions: Our study suggests that long term bisphosphonate therapy improves lumbar BMD and prevents increase in bone fragility fracture rate. Additionally it improves hypercalcaemia in PHPT.

Share and Cite:

Segula, D. , Nikolova, T. , Marks, E. , Ranganath, L. and Mishra, V. (2014) Long Term Outcome of Bisphosphonate Therapy in Patients with Primary Hyperparathyroidism. International Journal of Clinical Medicine, 5, 829-835. doi: 10.4236/ijcm.2014.514111.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Tierney, L.M., McPhee, S.J. and Papadakis, M.A. (2006) Current Medical Diagnosis and Treatment. McGraw-Hill Professional, 901.
[2] Melton Jr., L.J. (2002) The Epidemiology of Primary Hyperparathyroidism in North America. Journal of Bone and Mineral Research, 17, N12-N17.
[3] Bilezikian, J.P., Khan, A.A. and Potts, J.T.J. (2009) Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Third International Workshop. Journal of Clinical Endocrinology and Metabolism, 94, 335-339.
[4] Fraser, W.D. (2009) Hyperparathyroidism. Lancet, 374, 145-158.
[5] Gray, A. (2012) Nonsurgical Management of Mild Primary Hyperparathyroidism—A Reasonable Option. Clinical Endocrinology, 77, 639-644.
[6] Melton, L.J., Khosla, S., Atkinson, E.J., et al. (1997) Relationship of Bone Turnover to Bone Density and Fractures. Journal of Bone and Mineral Research, 12, 1083-1091.
[7] Sankaran, S., Gamble, G., Bolland, M., et al. (2010) Skeletal Effects of Interventions in Mild Primary Hyperparathyroidism: A Meta-Analysis. Journal of Clinical Endocrinology and Metabolism, 95, 1653-1662.
[8] Rodan, G.A. and Fleisch, H.A. (1996) Bisphosphonates: Mechanism of Action. Journal of Clinical Investigation, 97, 2692-2696.
[9] Black, D., Cummings, S., Karpf, D., Cauley, J.A., Thompson, D.E., Nevitt, M.C., et al. (1996) Randomised Trial of Effect of Alendronate on Risk of Fracture in Women with Existing Vertebral Fractures. Lancet, 348, 1535-1541.
[10] National Institute for Health and Clinical Excellence (2011) Osteoporosis—Secondary Prevention including Strontium Ranelate. Alendronate, Etidronate, Risedronate, Raloxifene, Strontium Ranelate and Teriparatide for the Secondary Prevention of Osteoporotic Fragility Fractures in Postmenopausal Women. Technical Appraisal 161.
[11] Compston, J., Cooper, A., Cooper, C., Francis, R., Kanis, J.A., Marsh, D., et al. (2009) Guidelines for the Diagnosis and Management of Osteoporosis in Postmenopausal Women and Men from the Age of 50 Years in the UK. Maturitas, 62, 105-108.
[12] Khosla, S., Burr, D., Cauley, J., Dempster, D.W., Ebeling, P.R., Felsenberg, D., et al. (2007). Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research. Journal of Bone and Mineral Research, 22, 1479-1491.
[13] Compston, J. (2011) Pathophysiology of Atypical Femoral Fractures and Osteonecrosis of the Jaw. Osteoporosis International, 22, 2951-2961.
[14] Silverberg, S.J., Shane, E., de la Cruz, L., et al. (1989) Skeletal Disease in Primary Hyperparathyroidism. Journal of Bone and Mineral Research, 4, 283-291.
[15] Rossini, M., Gatti, D., Isaia, G., et al. (2001) Effects of Oral Alendronate in Elderly Patients with Osteoporosis and Mild Primary Hyperparathyroidism. Journal of Bone and Mineral Research, 16, 113-119.
[16] Khan, A.A., Bilezikian, J.P., Kung, A.W., et al. (2004) Alendronate in Primary Hyperparathyroidism: A Double-Blind, Randomized, Placebo-Controlled Trial. Journal of Clinical Endocrinology & Metabolism, 89, 3319-3325.
[17] Grey, A.B., Stapleton, J.P., Evans, M.C., et al. (1996) Effect of Hormone Replacement Therapy on Bone Mineral Density in Post-Menopausal Women with Mild Primary Hyperparathyroidism. A Randomized, Controlled Trial. Annals of Internal Medicine, 125, 360-368.
[18] Selby, P.L. and Peacock, M. (1986) Ethinylestradiol and Norethindrone in the Treatment of Primary Hyperparathyroidism in Postmenopausal Women. New England Journal of Medicine, 314, 1481-1485.
[19] Khosla, S. and Melton III, J. (2002) Fracture Risk in Primary Hyperparathyroidism. Journal of Bone and Mineral Research, 17, N103-N107.
[20] Cranney, A., Guyatt, G. and Griffith, L. (2002) Osteoporosis Methodology Group and the Osteoporosis Research Advisory Group. Meta-Analyses of Therapies for Postmenopausal Osteoporosis. IX: Summary of Meta-Analyses of Therapies for Postmenopausal Osteoporosis. Endocrine Reviews, 23, 570-578.
[21] Holvik, K., Ahmed, L.A., Forsmo, S., et al. (2013) Low Serum Levels of 25-Hydroxyvitamin D Predict Hip Fracture in the Elderly: A NOREPOS Study. Journal of Clinical Endocrinology & Metabolism, 98, 3341-3350.
[22] Heike, A., Bischoff-Ferrari, P.H., Walter, C., et al. (2012) A Pooled Analysis of Vitamin D Dose, Requirements for Fracture Prevention. New England Journal of Medicine, 367, 40-49.
[23] Moosgaard, B., Christensen, S.E., Vestergaard, P., et al. (2008) Vitamin D Metabolites and Skeletal Consequences in Primary Hyperparathyroidism. Clinical Endocrinology, 68, 707-715.
[24] Grey, A., Lucas, J., Horne, A., et al. (2005) Vitamin D Repletion in Patients with Primary Hyperparathyroidism and Coexistent Vitamin D Insufficiency. Journal of Clinical Endocrinology and Metabolism, 90, 2122-2126.
[25] Berenson, J.R. (2002) Treatment of Hypercalcemia of Malignancy with Bisphosphonates. Seminars in Oncology, 29, 12.
[26] Bilezikian, J.P. (1993) Clinical Review 51: Management of Hypercalcemia. Journal of Clinical Endocrinology & Metabolism, 77, 1445.
[27] Khanna, A. (2006) Acquirednephrogenic Diabetes Insipidus. Seminars in Nephrology, 26, 244-248.
[28] Yu, N., Leese, G.P., Smith, D., et al. (2011) The Natural History of Treated and Untreated Primary Hyperparathyroidism: The Para-Thyroid Epidemiology and Audit Research Study. Quarterly Journal of Medicine, 104, 513-521.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.