Effects of Lithium Therapy on Bone Mineral Metabolism: A Two-Year Prospective Longitudinal Study¹

Abstract

Many studies showed an increased occurrence of primary hyperparathyroidism during lithium therapy. We studied 53 patients receiving lithium therapy prospectively for 2 yr. Serum PTH levels were unequivocally elevated. The baseline PTH level was 2.8 +/- 1.2 pmol/L and increased progressively to 3.9 +/- 1.5 pmol/L after 2 yr (P < 0.0005). There was no change in serum calcium, alkaline phosphatase, inorganic phosphate concentrations or tubular reabsorption of phosphate in relation to glomerular filtration rate. Fasting urinary reabsorption of calcium increased significantly (P < 0.0005), which was concordant with the PTH change. Fasting and 24-h urinary excretion of calcium decreased significantly (P < 0.0005), suggesting reduced, rather than enhanced, bone resorption as in primary hyperparathyroidism. This may be the main mechanism in maintaining normocalcemia, despite PTH elevation, during lithium therapy.

Lithium use and bone health in women with bipolar disorder: A cross‐sectional study

“…The unexpected finding led authors to postulate that "a counterregulatory factor" offset the hypercalcemic action of PTH by reducing bone resorption and that lithium was responsible. 21 This is an important mechanistic finding that deserves further exploration in light of recent research.…”

“…However, the authors found that lithium significantly decreased calcium urinary excretion and reduced calcium net balance, opposite effects that were expected with high levels of PTH as seen in primary hyperparathyroidism. The unexpected finding led authors to postulate that “a counterregulatory factor” offset the hypercalcemic action of PTH by reducing bone resorption and that lithium was responsible 21 . This is an important mechanistic finding that deserves further exploration in light of recent research.…”

Characterization of Calcium Homeostasis in Lithium‐Treated Patients Reveals Both Hypercalcaemia and Hypocalcaemia

“…Typically, pHPT is characterized by moderate-to-high serum calcium and PTH, This number includes seven half glands that were extirpated d Three histopathological diagnoses could not be recovered from medical records hypercalciuria and reduced levels of phosphate, though other variants exist such as normocalcaemic hyperparathyroidism [7,17]. Biochemically, LHPT is somewhat different: serum calcium can range from normal to moderately elevated, PTH ranges from normal to high (and often inappropriately high in relation to serum calcium), phosphate is normal to moderately elevated, and lastly, urinary secretion of calcium is low or very low (Table 2) [5,9,18,19]. Many individuals with pHPT have osteopenia or even osteoporosis, while it is suggested that lithium may have a protective effect on the skeleton [20].…”

Lithium induced hypercalcemia: an expert opinion and management algorithm

“…Lithium increases PTH most often associated with hyperplasia of all four parathyroid glands. Lithium associated hyperparathyroidism may differ in several ways from primary hyperparathyroidism (Berger et al 2013;Mak et al 1998;Meehan et al 2020). Some of these differences may also account for the potential bone-protective properties of lithium (Köhler-Forsberg et al 2022).…”