Elsevier

Bone

Volume 44, Issue 2, February 2009, Pages 331-334
Bone

Lithium's effect on bone mineral density

https://doi.org/10.1016/j.bone.2008.10.001Get rights and content

Abstract

Lithium salts are widely used in treating psychiatric patients. Lithium may be associated with hyperparathyroidism, a risk factor for osteoporosis. However, the data on the effect of lithium on bone mass are conflicting. We assessed bone mineral density with dual-energy X-ray absorptiometry at the hip and lumbar spine in 75 lithium treated outpatients and 75 normal subjects matched for age, sex and body mass index. Serum total calcium, intact parathyroid hormone (PTH), estradiol, osteocalcin, total alkaline phosphatase (ALP) and C-telopeptide (CTX) in addition to fasting urinary calcium excretion were also determined in both groups. The mean (± SD) bone density in lithium treated patients was 4.5% higher at the spine (P < 0.05), 5.3% higher at the femoral neck (P < 0.05) and 7.5% higher at the trochanter (P < 0.05). In addition, lithium treated patients had lower serum total ALP (P < 0.005), lower serum osteocalcin (P < 0.005) and lower serum CTX (P < 0.05) but the total calcium, PTH and urinary calcium excretion did not differ significantly between patients and controls. In conclusion, our results suggest that maintenance therapy with lithium carbonate may preserve or enhance bone mass. These data also suggest a lower bone turnover state in those receiving lithium.

Introduction

Lithium, widely used in the management of bipolar and other psychiatric disorders, has a complex effect on calcium homeostasis. It has been shown that lithium therapy may be associated with a mild, reversible hyperparathyroid state [1], [2], [3], [4], [5], [6]. Also it may affect calcium transport, both at the level of the renal tubule and the gut, which is probably not mediated by stimulation of parathyroid activity [7].

Continuously elevated PTH, as is seen in primary hyperparathyroidism, is a major risk factor for bone loss. On the other hand, PTH has an anabolic effect when administered intermittently [8]. Depending on the exact, yet not completely elucidated, nature of alterations in PTH secretion in treated patients, lithium may have the potential of accelerating or retarding bone loss theoretically. Moreover, lithium may affect bone independently. Lithium chloride inhibited the osteoid synthesis leading to a decreased bone mineralization in rat [9]. Another experimental study showed anabolic effect of lithium on bone mass in mice [10]. No histomorphometric examination of bone in treated patients with lithium has been reported and few studies that conducted about the effects of lithium on bone density have produced inconsistent results [2], [5], [11], [12], [13].

Therefore, we selected a large group of outpatients on lithium maintenance therapy to investigate the effect of lithium on bone mass. Furthermore, we evaluated the bone turnover indices in these patients.

Section snippets

Materials and methods

All subjects on lithium maintenance therapy who consecutively referred to psychiatric outpatient clinic were invited to take part in this study. Patients were excluded if they had known risk factors for decreasing bone density including history of menopause or oligoamenorrhea, heavy cigarette smoking, other illnesses that could affect the bone or taking medications [14] known to influence calcium metabolism or bone mass; also excluding were those with abnormal renal or thyroid function test (

Results

Table 1 shows demographic data and corresponding serum and urine biochemical indices for both groups. The average duration of lithium therapy was 8.2 (± 5.7) years with a range of 1–23 years.

The corrected total Ca and PTH levels of the patient group were not statistically different from those of control subjects. The mean serum ALP, CTX and osteocalcin were significantly lower in lithium treated patients than their controls while UcaE was identical in both groups. No correlation was found in

Discussion

We found that patients on maintenance therapy with lithium had higher bone mineral density in both the lumbar spine and the proximal femur and lower serum ALP, CTX and osteocalcin than normal controls. The lower serum osteocalcin, CTX and ALP suggest decreased bone remodeling contrary to what is seen in primary hyperparathyroidism, which is associated with accelerated skeletal turnover and increased osteocalcin and markers of bone resorption. Individuals with higher rates of bone turnover have

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